The Future BRH welcomed the opportunity to reflect on its progress and achievements during it’s mid-term review in Q1 2023 and was delighted by the very positive panel feedback. In this brochure we aim to capture some of the highlights from the 2023-24 period, provide a high-level snapshot of key developments related to UK biomanufacturing and a forward perspective for the Hub.
Future BRH has seen the intensification of our research programmes and development of new technology platforms for biomanufacturing both within the Hub (Manchester) and across the Spoke institutions, with new partnerships and extended programmes with industry members, and exciting new capabilities.
We will highlight the development of key technology platforms and how we are applying these in sector-focused projects towards delivery of biomanufacturing solutions. Future BRH is addressing the two grand challenges of ‘SPEED’ and ‘COST’, accelerating biocatalyst delivery for biomanufacturing solutions, and reducing the cost associated with delivering these applications at scale (using flow biocatalysis and fermentation-based technologies). An important key element to success has been working with industry partners to explore and de-risk biomanufacturing technologies at low technology readiness levels (TRL 1-3), prior to subsequent scale-up and adoption by industry partners at higher TRLs.
THE HUB IS ACCELERATING THE DELIVERY OF CHEMICALS BIOMANUFACTURING IN THE
UK
Future BRH continues to work as an interconnected network of UK research strength in the field of biomanufacturing. Once again, we have seen the development of our researchers’ careers and welcomed new additions to the research teams at Hub and Spoke sites. Exciting developments across the Future BRH include our new spoke partnership with the University of Keele and the launch of the UCL East campus with its Manufacturing Futures Lab.
EXECUTIVE SUMMARY
Throughout 2023-24 Future BRH has focused on developing emerging technologies and foundational science that will transition incumbent petrochemicals industries towards sustainable biomanufacturing. Accelerated enzyme, organism and process engineering methods require new tools and technologies that will ultimately lead to more rapid process delivery, and this has been a primary focus in the first half of the 7-year funding.
A directed evolution end-to-end innovation cycle has been established that harnesses automation platforms and HTP data generation connecting in-silico learn (ML and AI) methods with structure-based approaches, completing the Design/Build/Test/Learn cycle and predictive engineering pipelines. Partnerships have now been established to enable utilization of large data sets and the use of metagenomics/structure prediction algorithms (e.g., alpha fold) to inform scaffold selections and drive rapid enzyme engineering.
Future BRH has focussed on the development of tools and technologies to work with industrial strains (e.g., Halomonas, Cyanobacteria) and pioneered in this space to provide comprehensive toolsets for strain engineering, the use of which has accelerated process development in selected cases (e.g., fuels; platform chemicals). These platforms are now available to industry partners and academic collaborators, helping to structure research efforts nationally in the use of industrial organisms in chemicals production. Examples include scale up of Halomonas for bioplastics production (UCL); fuels production (C3 Biotech); and monomers for polymers (UoM).
The circular bioeconomy has been supported by the growth of a new ‘circular degradation theme’ within Future BRH. This extends current capabilities beyond ‘make/build’ activities. An example includes an ONRG/Airbus collaboration in composite materials recycling for the biomanufacture of new materials.
Future BRH is now embedding these technology innovations into the burgeoning UK manufacturing landscape through partnership and collaboration, working with industrial partners to advance processes through the TRL’s and provide industrial partner support in process de-risking.
Future BRH will continue its tools and technologies innovation programmes to strengthen UK capacity in enzyme, microbial strain, and process engineering. With partners the delivery of processes at higher TRL will lead to technology development (pilots/demonstrators) and commercialisation.
FUTURE BRH HARNESSING UK STRENGTHS IN BIOMANUFACTURING
Through its Hub and Spoke model, FutureBRH provides unique opportunities to unite UK-wide knowledge and capabilities across the whole biomanufacturing pipeline in interdisciplinary programmes and inter-sector collaborations with industry to build UK capacity.
ACADEMIC PARTNERS
Synthetic Biology (SYNBIOCHEM), Biocatalysis, Analytics, Automation, AI
Biochemical Engineering, High Throughput Bioprocess Development
Techno-Economics, Life Cycle Analysis, Process Design, Reaction Efficiencies
Synthetic Biology, Engineering Biology for Biomanufacturing
INNOVATION CENTRES AND SCALE-UP FACILITIES
Innovation and Knowledge Centre for Synthetic Biology, Accelerating Technology Commercialisation
De-risking Scale-up. Driving Industry-Academic Interactions in IB. Training for a Skilled Workforce
Leading UK Technology Innovation Centre, Supply Chains and Scale-up for Full-scale Production Processes
By partnering academic excellence with innovation centres and scale-up facilities, the Future BRH is bridging the gap between academic discovery, innovation, and commercialisation, to understand the risks and strategies needed to support the industrialisation of biomanufacturing towards full scale production.
The Hub is based within the Manchester Institute of Biotechnology (MIB) at the University of Manchester (UoM) where its research programme forms a central part of the UoM Biotechnology research beacon, building on world leading IB expertise and benefitting from state-of-the-art infrastructure. Spoke partner academic Centres of Excellence; University College London (UCL), Imperial College London (ICL); University of Nottingham (UoN); and University of Keele (UoM); provide complementary expertise in the IB and biomanufacturing space, alongside the innovation centre IBioIC and large-scale facilities at CPI, to collectively accelerate delivery of sustainable biomanufacturing solutions.
A core team of researchers based at Manchester oversee the diverse research portfolio with a growing cohort of PhD students, supported by the core management team.
Executive Management Team: Brings leadership from across the Hub and Spoke partners to the Future BRH. External Advisory Board: Future BRH is grateful for the continued support of its EAB who have provided critical advice and support throughout.
NEW SPOKE PARTNER – UNIVERSITY OF KEELE
Future BRH welcomed Keele as a new spoke in September 2022. The University is known for its focus on multi-disciplinarity, historically awarding undergraduate degrees as dual honours, with this also reflected in the research that is conducted there. In the school of chemical and physical sciences, the group headed by Sebastian Cosgrove (Future BRH alumnus) has a strong research focus on bioprocess development, with enzyme immobilisation playing a key role. The lab has capability to perform a host of continuous reactions with dedicated flow systems which include high-precision high pressure HPLC pumps, fraction collector, column heating, and a recently modified benchtop NMR spectrometer which can permit inline analysis.
A recent biomanufacturing case study in collaboration with Prof. Gavin Miller (Director of Keele Centre for Glycoscience Research and Training) demonstrated that a bio-based alkyl polyglycoside product could be bioremediated using an immobilised alcohol oxidase. Typically, high pressure distillation is applied to remove excess long-chain alcohol solvents from the synthesis of these bio-based surfactants, which can result in degradation of the product. By switching to an enzymatic, ambient oxidation of the long chain alcohol by-product to the aldehyde, this could be removed with a resin to avoid high temperature distillation.
The Glycoscience centre has a range of activities which overlap with biomanufacturing, including research programmes aligned with Future BRH partners including Unilever, CRODA, Johnson Matthey and AstraZeneca. Ongoing projects include understanding and modifying properties of carbohydrates for industrial applications, the continuous synthesis of modified sugar nucleotides for biomedical and materials studies, and the discovery of nucleic acid modification enzymes to allow for the facile enzymatic production of modified nucleosides.
Publication: Wahart, Dolan, Anderson, Ní Cheallaigh, Staniland, Lima, Skidmore,
Cosgrove
a Biocatalyst to Bioremediate the Purification of Alkylglycosides ChemBioChem. 25, e202300625.
IMPERIAL COLLEGE LONDON AND SynBiCite
Short term collaboration projects with Imperial College provided the opportunity to work with new academics, whilst the SynBiCite run SynBiTECH conference provided a superb opportunity to hear about synthetic biology innovation. The event brought together visionary leaders and industry expert.
It was great to hear Nigel Scrutton tell us more about C3 Biotech’s journey from early discovery research at Manchester University through to the building of its scale up facility in Stockport.
Miller,
(2023) Harnessing
UCL EAST AND THE MANUFACTURING FUTURES LAB
The security of longer-term funding through the FBRH has helped colleagues at UCL secure institutional investment in the new UCL East Manufacturing Futures Lab (MFL). This is part of UCL’s strategic development of a new UCL East campus on the Queen Elizabeth Olympic Park and will contribute to the wider UK Industrial Biotechnology and Engineering Biology ecosystem.
(A) The UCL East Marshgate building, adjacent to the Olympic Stadium, is home to the Manufacturing Futures Lab (MFL). The MFL research Pods are spread across the top two floors of the building.
(B) The research Pods on the 7th floor (Red) focus on chemical and pharmaceutical synthesis while the teaching laboratories (Blue) support MFL MSc programme delivery.
The MFL opened in September 2023 and focuses on the sustainable manufacture of chemicals, pharmaceuticals, and materials. Research activity is supported by 15 new academic posts across the UCL departments of Biochemical, Chemical and Mechanical Engineering and Chemistry. The MFL provides nearly 2000m2 of dedicated research space and sits alongside new teaching laboratories used for delivery of six new MFL MSc programmes. These research and teaching facilities are supported by 10 technical staff each with specialist expertise.
Research within the MFL occurs within six specially designed research ‘Pods’ each equipped to support specialised, multi-disciplinary research activity. The Integrated Synthesis Pod brings together work on enzyme and chemical catalysts and multi-step, chemo-enzymatic syntheses. Dr Jack Jeffries (UCL Biochemical Engineering) leads work on enzyme discovery and is a Co-I in the recently awarded BBSRC Engineering Biology Mission Hub on Preventing Plastic Pollution. Dr Michele Crotti and Dr Daniele Castagnolo (both UCL Chemistry) lead work on enzyme evolution and chemo-enzymatic syntheses respectively. Dr Castagnolo is Programme Director of the MFL MSc in Chemical Sustainability.
Work in the Bioprocessing Pod brings together the activity of two FBRH Co-Is, Prof. Gary Lye (MFL Director) and Prof. Alex Conradie (both UCL Biochemical Engineering). This Pod is designed to support work on the design, optimisation and scale-up of fermentation-based processes and the downstream processing of novel enzymes and chemical products. Prof. Conradie leads a new BBSRC Prosperity Partnership grant with Unilever, which looks at decarbonising surfactant production, and involves collaboration with Prof. Rob Field at the Manchester Institute of Biotechnology (MIB).
Research in the Continuous Processing Pod is led by Dr Max Besenhard (UCL Chemical Engineering) who brings expertise in continuous flow reactors and automation for chemical process development. Dr Besenhard is Programme Director of the MFL MSc in Digital Manufacture of Advanced Materials. Another Chemical Engineering colleague, Dr Diego Lopez Barreiro, leads MFL research on the use of biopolymers in the manufacture of functional materials.
The support of early career researchers is a key MFL priority. Early success has been achieved by the award of a UKRI Future Leaders Fellowship to Dr Emily Kostas (UCL Biochemical Engineering) who joined the MFL staff in February 2024. Her fellowship, SEACONOMY, aims to develop biorefinery technologies to facilitate development of a UK seaweed bioeconomy. This involves collaboration with another UCL-based FBRH investigator, Dr Marco Marques, on the development and scale-up of continuous flow biorefinery technologies.
MFL activities will thus enable continued growth of the sector and ensure provision of the skilled individuals needed at all levels.
(C) The Intensified Processing Pod allows study of downstream processing operations at pilot scale and complements the existing pilot scale fermentation facilities at the main UCL Bloomsbury campus.
The Bioprocessing, Rapid Prototyping and Nanoscale Manufacturing Pods are located on the 8th floor.
IBioIC CELEBRATES ITS 10TH ANNIVERSARY
Future BRH was delighted to participate in IBioIC’s 10th Annual Conference which provided an opportunity to reflect on the transformation of the IB sphere over the past 10 years, celebrate key success stories and look to the next 10 years to identify what transformations will, and need to, happen across technology, policy, infrastructure, and research. The team engaged with various audiences and a few of those have had follow-up visits at MIB.
Established in 2014, IBioIC fulfils the aims of the National Plan for Industrial Biotechnology and grow the IB sector in Scotland. It has supported this growth by helping to attract £35 million of additional funding for R&D, supported more than 260 start-ups, small businesses, and established companies to develop new bio-based processes and products. IBioIC has delivered nearly 500 PhD, MSc and HND’s and over 200 scale-up trainees, helping to create a thriving bioeconomy in Scotland.
(D)
INDUSTRIAL PARTNERS
Future BRH works in partnership with a growing number of core industrial partners to address industrial needs and accelerate delivery, translation, and application of biomanufacturing technologies, and support transition to more sustainable biomanufacturing production processes.
To date, Future BRH has 15 Core Partners generating financial contributions (both cash and in-kind) that have funded confidential ‘proof-of-concept’ research projects to evaluate new approaches to industry specific challenges, carried out by PDRA staff and supported by the core FutureBRH team, with new projects in discussion. Core Industry Partners have joined “deep dive” science workshops (e.g., directed evolution 28/06/22, and industry days 16/10/23 with access to Future BRH landscaping documents (e.g., biomanufacturing chemical targets, host strains, feedstocks, and processes) and informed wider discussions and development of the science portfolio (e.g., end of life recycling). Industry collaborations and co-supervision of PhD studentships have been another significant route by which industry partners have contributed towards the Future BRH science programme. To date we have 10 studentships supported in this way.
FUTURE BRH INDUSTRY WORKSHOP
The Future BRH industry workshop in October 2023 provided a great opportunity to celebrate the successful partnerships and collaborations by bringing stakeholders, especially industrial partners together in the Manchester Institute of Biotechnology. The day was full of activities and engagement that witnessed interesting discussions and deep conversations around technicalities and challenges of the ever-growing biotechnology landscape within the UK, especially the North-West, reaffirming the importance of the sector for future sustainability and access to important bio-based resources.
SCIENTIFIC VISION
The Future BRH was established to deliver the UK Government flagship policy ‘Innovation Nation’ in the biomanufacturing sector by accelerated delivery of economically attractive, robust, and scalable bio-based manufacturing to meet these urgent societal needs and commercial demand in four key industrial sectors:
These developments will help accelerate the industrialisation of biology and biomanufacturing providing transition pathways to sustainable manufacturing, clean growth, and net zero economies which will support the emergence of a Bioeconomy that will place the UK at the forefront of global economic Clean Growth.
Future BRH is addressing the entire biomanufacturing lifecycle, and has continued to focus on the sector-defined Grand Challenges faced in delivery of biomanufacturing solutions, that of addressing the speed of development of robust biobased parts (enzyme engineering as enablers of biomanufacturing) and their integration for product delivery through process development and translating these solutions into cost effective biomanufacturing applications at scale (implications for scaled production; economics).
Accelerated development and integration of biocatalyst engineering
Realising the value of Industrial Biotechnology at scale
To tackle these challenges the Hub has developed and integrated activities across 5 key technology platforms whilst applying these in sector focused projects in partnership with industry.
SECTOR SPECIFIC APPLICATION: TAILORED BIOMANUFACTURING SOLUTIONS
3. Continuous flow Biocatalysis and Immobilization
SCIENTIFIC FOCUS
Future BRH research tackles challenge-based projects embracing a holistic approach to biomanufacturing at multiple scales, from delivery of new parts (e.g., enzymes) and devices (e.g., pathways; regulatory circuits) in the context of in vivo microbial strain engineering and in vitro cascades, to methods for down-stream processing (DSP) and techno-economic analysis (TEA) of complete biomanufacturing systems.
Connecting these multi-scale approaches ensures that delivery of large-scale biomanufacturing platforms is best served by early-stage research programmes at the enzyme, microorganism, and laboratory reactor scales.
COMPLEMENTARY TECHNOLOGY PLATFORM RESEARCH THEMES
THEME 1 - HIGH THROUGHPUT BIOCATALYST ENGINEERING
This theme is aimed at speeding up the discovery and delivery of novel and optimised enzymes for biomanufacturing by developing high throughput (HTP) methods and workflows, including directed evolution and intelligent / rational design, harnessing where possible laboratory automation and data-driven approaches. Engineered biocatalysts are then applied within Future BRH platforms for in vitro and in vivo chemicals production.
Research has included:
• Improvement of monoterpene synthases towards designer terpene synthases and pure products (recently scaled to 4000L by industry partner C3 BIOTECH)
• Development of more stable light dependent photo-biocatalysts (e.g., fatty acid decarboxylases) used in synthetic fuels manufacture
• Engineering improved properties and repurposing of other thermal and light-driven enzyme reactions
• Enzyme engineering for the biomanufacture of Active Pharmaceutical Ingredients (APIs) and monomers for polymer manufacturing
Platform technology development for robust automated workflows.
A key focus since the installation of our fully integrated automation platform (Supported through the Royce Institute for Advanced Materials) has been developing fully automated workflows for enzyme evolution.
DECODING CATALYSIS BY TERPENE SYNTHASES
Terpenoids comprise a large family of natural products with broad structural diversity, and over 100,000 compounds described in the Dictionary of Natural Products. Terpenoids are valuable industrial targets with applications as flavours and fragrances, precursors for pharmaceuticals and bioplastics, as well as next-generation biofuels. Efforts have been made to bio-manufacture terpenoids using engineered microbial hosts. However, titres are often low and consist of product mixtures due to the promiscuous nature of terpene synthases (TSs), which catalyse the final step in terpenoid biosynthesis.
TSs catalyse the seemingly simple conversion of linear isoprenoid pyrophosphate precursors into complex cyclic molecular structures, with the final products often containing multiple stereo-centres. After reaction initiation, which releases the pyrophosphate, the enzyme ‘manages’ the resulting high-energy carbocation intermediates by providing a hydrophobic ‘mould’, which subtly guides these intermediates to their final products whilst avoiding branching and pre-mature quenching. Detailed understanding of TS reaction cascades and residues allows redirection via protein engineering, to alternative products and higher value terpenoids.
Future BRH has studied a range of TSs from different sources (including plants, bacteria, and fungi) using a combination of structural biology, computational chemistry and modelling, and high-throughput activity screening and product profiling of TS variants, to understand the complexities of TS catalysis. We uncovered a range of catalytic motifs that control product outcome in TSs towards a more general understanding of TS chemistry. The identified motifs provide attractive engineering targets to alter TS product profiles with relatively few amino acid changes. We will apply data-driven methods (e.g., machine learning) for rational and predictive engineering towards “designer terpene synthases”, which will begin to emerge as a realistic goal.
Recent Publications:
• Leferink, Scrutton, (2022) Predictive engineering of class I terpene synthases using experimental and computational approaches. Chembiochem, 23 (5), e202100484.
• Whitehead, Leferink, Komati Reddy, Levy, Hay, Takano, Scrutton, (2022) How a 10-epi-cubebol synthase avoids premature reaction quenching to form a tricyclic product at high purity. ACS Catalysis, 12 (19), 12123-12131.
Florence Hardy (Anthony Green Lab): Last spring I received a Future BRH Academic Feasibility Study Grant, which enabled a 3-month secondment to the University of Washington, to work with Professor David Baker at the Institute for Protein Design. During the trip I was trained by world leaders in the field of computational protein and enzyme design. Using state-of-the-art computational methods, I was able to computationally design a portfolio of light activated photoenzymes that are capable of catalysing valuable reactions currently not found in nature. This experience was invaluable to my training and has led to some very exciting results in collaboration between the Manchester Institute of Biotechnology and the Institute for Protein Design.
Ashleigh Burke’s collaboration project with GSK highlighted in our 2022 report resulted in a 'hot article' research paper - Burke, Lister, Marshall, Borown, Lloyd, Green & Turner. (2023). Engineering of biocatalysts for enantioselective reductive aminations of cyclic secondary amines. ChemCatChem. 15, e202300256.
THEME 2 - HIGH THROUGHPUT ANALYTICAL SCREENING
Fast and reliable screening methods for detailed characterisation are essential to the delivery of novel parts, pathways, and processes for biomanufacturing. The development of HTP screening technology platforms, data management and integration, and machine learning are central to this theme. These analytical platforms have been developed for:
• Establishment of generic ultra HTP screening, mutagenesis, and sequencing methods for biomanufacturing applications
• Production of valuable terpenes (Value Added Chemicals; Synthetic Fuels) through the engineering of monoterpene synthases
• Proteomics characterisation of emerging industrial biomanufacturing host strains, including the Future BRH focus on Halomonas
UNDERSTANDING AND DEVELOPMENT OF BASE STRAINS FOR INDUSTRIAL PRODUCTION
Omics characterisation of Future BRH host strains will inform strain engineering, production pathway optimisation and delivery at scale. Cost reduction in biomanufacturing development requires rapid characterisation of novel host cell isolates with desirable characteristics and rapid realisation of production pathways in both the novel, and established, host strains. We have implemented an omics pipeline capable of genomics characterisation (PacBio sequencing) of novel strains and quantitative proteomic analysis of chassis under biomanufacturing conditions. The insight afforded by these methods enable intelligent design decisions for both production pathways, and bioreactor conditions.
Having established proteomics workflows for bacteria, Future BRH is applying these analytical tools to gain insight into the internal production mechanisms that bacteria use to inform industrial development. Our workflows can quantify most expressed proteins, providing coverage of core and carbon metabolism of E. coli. We are now applying this approach to photosynthetic cyanobacteria Synechocystis to identify proteomic states associated with maximum CO2 conversion to product. Mechanistic insights will be used to identify genome interventions and optimisation of growth conditions to increase product yield.
EXEMPLAR PUBLICATIONS:
• Russell, M. Baseline Proteomics Characterisation of Biomanufacturing Organism Halomonas Bluephagenesis. http://dx.doi.org/10.6019/PXD030494.
• Baseline proteomics characterisation of the emerging host biomanufacturing organism Halomonas bluephagenesis (2022) Russell, Currin, Rowe, Chen, Barran & Scrutton. Sci Data 9, 492 DOI: 10.1038/s41597-022-01610-0
The Future BRH has embedded the SYNBIOCHEM pipeline into its research portfolio and is applying this to diversification of alkaloid production pathways towards a combined in vivo / in vitro approach for the biosynthesis of natural and semi-synthetic morphinan alkaloids.
Future BRH projects are now benefitting from this pipeline including debugging terpene synthesis pathways, expanding our access to morphinan alkaloids, and extending flavanone diversity.
Future BRH funded proof of concept (PoC) projects to develop wider collaborations which included:
UCL: PoC project led by Jack Jeffries explored the development of cell free expression systems for large scale enzyme library production. This project aimed to use cell free DNA and protein synthesis to scale down enzyme production for use in biocatalytic assays. It tested the feasibility of using these to express and assay a large scale (metagenomic or mutagenesis) enzyme library.
Imperial College London: PoC project (Alexander Webb, Richard Kelwick and Paul Freemont) OMEGA: Outer Membrane vEsicle enGineering and mAnufacturing. Bacteria naturally shed outer membrane vesicles (OMVs) that are tiny molecular packages containing proteins, fats, and other molecules. OMVs are attractive for use as vaccines and therapeutics because of their ability to interact with host cells and their natural immunogenic properties (DOI:10.20517/evcna.2023.21).
To help accelerate next generation OMV therapeutics we are developing the OMEGA platform technology to create better and scalable methods for manufacturing new kinds of vaccine or therapeutic OMVs. The FBRH funding allowed the Imperial team to further validate their OMEGA OMV manufacturing workflows, build new collaborations and apply for additional funding.
Related manuscripts:
1. Kelwick RJR, Webb AJ, Freemont PS. (2023). Opportunities for engineering outer membrane vesicles using synthetic biology approaches. Extracell Vesicles Circ Nucleic Acids 4:255–61. [DOI: 10.20517/evcna.2023.21].
2. Kelwick RJR, Webb AJ, Freemont PS. Accelerating extracellular vesicle research and biotechnological applications using synthetic biology approaches. [Focus Manuscript submitted]
THEME 3 - CONTINUOUS FLOW / CASCADE BIOCATALYSIS
This theme has focussed on the development of enzyme immobilisation technologies and the engineering of cost-effective and renewable immobilisation scaffolds for use in modular, continuous flow reactor systems that can be used at bench scale (e.g., for the biomanufacture of APIs, Pharmaceuticals) or larger scales (for Value Added Chemicals).
Research has explored the use of immobilised biocatalysts in continuous flow, seen the development and patenting of novel sustainable macromolecular scaffolds for flow catalysis, and new Spoke activity at Keele University (UoK). UCL research programmes have addressed the miniaturisation of flow systems through modular micro-reactor designs suitable for small scale biocatalytic manufacture. Outcomes are therefore biomanufacturing formats in flow at different scales that can be tailored to sector specific needs.
UCL PROJECTS
Future BRH members at UCL have developed a modular microreactor platform for continuous enzymatic biocatalysis, designed and fabricated using common and advanced fabrication methods. This system allows easy biocatalyst insertion with minimal changes (by only moving a single part of the overall assembly) and offers the opportunity for wider adoption of microreactor technology in industrial assets.
The microreactor supports a variety of biocatalyst immobilisation modes, enabling versatile biotransformations and has been successfully tested as a microreactor with biocatalysts entrapped into hydrogel sheets and as a packed bed microreactor utilising commercial preparations. This is now being expanded to a wider range of biotransformations and combining single units to create enzymatic cascades to access added-value products. The latest publication showcases the standard device that can be used to culture diverse cell lines and perform biocatalysis with free or immobilised enzymes.
Publication highlight: Bajić, Khiawjan, Hilton, Lye, Marques, & Szita, (2024), A paradigm shift for biocatalytic microreactors: Decoupling application from reactor design. Biochem Engin. J., 205, 109260, https://doi.org/10.1016/j.bej.2024.109260.
THEME 4 - INDUSTRIAL HOST STRAIN ENGINEERING
Biomanufacturing at scale requires robust ‘industrialised’ host production strains with predictive engineering approaches for their modification. This theme has focused on the development of base strains for industrial microbial hosts for sector-specific applications and scale-up. High performance gateway pathways and tool development.
Prototyping in E. coli: Base E. coli strains have been engineered for improved performance and high-titre production of multiple targets including hydrocarbons, terpenes, plastic precursors, flavonoids, and APIs. Application of the SYNBIOCHEM Design/Build/Test/Learn pipeline for diverse chemical targets included de novo production of gate-keeper flavanones which has been extended through industry projects focused on flavonoid-derived therapeutics.
LOW-COST PRODUCTION HOSTS: HALOMONAS
Future BRH has developed a suite of engineering tools to facilitate the creation of robust industrial host strains including Halomonas sp. Development of such robust halophilic hosts has the potential to dramatically reduce both capital and operational costs of biomanufacturing due to their ability to grow under non-sterile production conditions, utilise waste biogenic feedstocks and seawater. Recent work demonstrated the potential for co-production of biofuels, bioplastics and biochemicals during extended fermentation.
Some of the current challenges in pilot- and industrial-scale bioproduction when using the extremophile bacteria Halomomas spp. under non-sterile conditions are considered in a recent review (Zhang et al).
Our latest proof of concept study illustrates the opportunities of recruiting environmental isolates as industrial hosts for chemicals biomanufacturing, where utilisation of CO2 could replace or augment the use of biogenic feedstocks in non-sterile industrial bioreactors.
Publication highlights:
• Zhang, Yan, Park, Scrutton, Chen & Chen. (2023). Non-Sterile Microbial Production of Chemicals based on Halomonas spp. Current Opinion in Biotechnology, 85, 103064 DOI: 10.1016/j.copbio.2023.103064
• Park, Toogood, Chen, & Scrutton. (2022). Co-production of biofuel, bioplastics and biochemicals during extended fermentation of Halomonas bluephagenesis. Microbial Biotech, DOI: 10.1111/1751-7915.14158
• Faulkner, Hoeven, Kelly, Scrutton, et al. (2023). Chemoautotrophic production of gaseous hydrocarbons, bioplastics and osmolytes by a novel Halomonas species. Biotechnol. Biofuels, 16, 152 https://doi.org/10.1186/s13068-023-02404-1
Work has enabled some of our industrial partners to develop plans for scaled bio-production platforms using strains engineered with some of these tools.
CO2 CAPTURE AS A FEEDSTOCK FOR BIOMANUFACTURING
This proof-of-concept study illustrates the value of recruiting environmental isolates as industrial hosts for chemicals biomanufacturing, where CO2 utilisation could replace, or augment, the use of biogenic feedstocks in non-sterile, industrialised bioreactors.
Future BRH partners at MIB and IBioIC are collaborating to scale-up and optimise novel routes to biological carbon capture and biomaterial production using the Flexbio facility at Heriot-Watt University. The 8x2L DASGIP parallel reactor system was used to define and optimise the parameters affecting growth and productivity of an engineered cyanobacterial host using design of experiment (DOE) principles, with the aim to produce biomaterials from CO2. Experiments so far have been a great success and have been used to create a predictive model suggesting optimum reactor conditions. The data will underpin future scale up efforts and form part of an upcoming academic publication. We hope that this project is but the first of many and look forward to many more successful collaborations facilitated by the Future BRH.
Thank you to Elise Viau
painstakingly retrofitting the DASGIP vessels with thousands of LEDs to provide the
YEAST STRAINS AS LOW pH PRODUCTION HOSTS
Future BRH has continued to collaborate with bp Biosciences Centre on developing non-conventional yeast strains. The projects have focused on species with potential as low pH production hosts for the biomanufacture of green chemicals, including organic acids and sophorolipids.
To accelerate strain development with Kazachstania spp and Starmerella spp, the characterisation of strains at the genetic, genomic, transcriptomic, and phenotypic level is required. Recent work provides a high-quality reference genome resource to advance fundamental knowledge of these non-conventional yeasts that will support the development of genetic tools for their strain engineering.
Balarezo-Cisneros, Timouma, Hanak, Currin, Valle, Delneri. (2023). High quality de novo genome assembly of the non-conventional yeast Kazachstania bulderi describes a potential low pH production host for biorefineries. Commun. Biol. 2023 Sep 7;6(1):918. doi: 10.1038/s42003-023-05285-0
(pictured left) and Emilia Cropper (pictured right) of FlexBio for their patience in
photosynthetic bacteria with light.
Circos Plot of Kazachstania bulderi CBS 8639 strain
THEME 5 - SCALED BATCH & FLOW FERMENTATION
Established to develop understanding of, and solve existing constraints on, biomanufacturing at scale, this theme is developing down-stream processes for targeted production, with a view to developing early proof of concept (experimental pilot) platforms and thus extending technologies beyond laboratory scale. Work in this theme involves research programmes at UoM, UCL and UoN, with scale up partners (IBioIC and CPI) for the development of both continuous and batch fermentation protocols at multiple scales, with process optimisation; and optimisation of downstream processes such as product recovery. An understanding of production challenges at scale is supported by TEA, sustainability assessments and considerations of Responsible Research and Innovation (RRI).
INTEGRATED BIOREACTOR PLATFORMS
Prototyping and high throughput strain engineering has largely been centred around small volume high throughput automation capabilities.
A key focus over the past year or two has been to move towards scaled delivery either through shake flasks or bioreactors at different scales. We are now looking to deliver a more automated scale up optimisation pipeline to complement the prototyping small volume discovery model of SYNBIOCHEM.
• BioLector/RoboLector parallel fermentation platform used to optimise fermentation parameters on a small scale (48 x 1-2 mL) using Design of Experiments
• Bench-scale (1-5L) fermentations used to optimise production conditions for E. coli and Halomonas
• New Ambr system for small scale parallel fermentations (6 x 250ml)
• 5L fermenter coupled to PTR-MS (BBSRC Alert) for rapid real-time analysis of gas phase volatiles during fermentation
• Development of efficient, cost effective and environmentally friendly DSP
A new ALERT funded facility in the lab of James Winterburn run by Robin Hoeven provides a superb capability to begin to optimise our production processes towards scale up, with 500ml and 4L bioreactors. The addition of 30L fermentation will complete this integrated bioreactor platform for rapid scale-up and translation.
Several members of the Future BRH research team recently undertook a short secondment collaboration with C3 Biotechnologies (Maritime and Aerospace) to help run a bacterial fermentation-based process developed in partnership with FBRH in the MIB, at Pilot scale ( 3m3), and to conduct performance tests for aviation biofuel production. Whilst Future BRH has previously supported training through UCL MBI masters in fermentation these secondments provided a great way to put theoretical knowledge into practice.
“This was a great opportunity to support the operation of large-scale fermenters and related pieces of equipment, as well as contributing to the downstream processing of the production steps.” - Mohamed Amer
“I found it incredibly exciting and rewarding to see a process I’ve help develop from the proof-of-concept stage, out in the real world at scale employing people and helping make the circular bioeconomy a reality. This experience of working closely with an SME has given me confidence to discuss, advise, consult, and collaborate with SME partners in the future, especially on fermentative processes and scale up.” - Matt Faulkner
TECHNO-ECONOMIC ANALYSIS
Several projects use TEA to understand production and capital costs, environmental impacts to inform bioprocess development, and understand the opportunities and challenges for production at scale. Work benefits from rigorous TEA activities at UCL (Conradie) and is applying conceptual process design and realistic biological, chemical, and engineering assumptions to create model frameworks for development of chemical targets and industrial hosts.
RESPONSIBLE RESEARCH AND INNOVATION
Ongoing RRI assessment of Future BRH projects has allowed deliberation of ethical, societal, regulatory and policy issues associated with biomanufacturing.
• Early, Rapid, Sustainability Assessment (ESRA) tool. Rapid, on-going project assessment and consideration of potential feedstocks and target compounds
• Development for application in biomanufacturing translation and scaling stages
• Societal deliberation, decision tools - RRI / RI in projects and policy
Policy work has included: Challenges of building up a bottom-up bioeconomy and the role of biofoundries as intermediaries.
Building the Bioeconomy: A targeted assessment approach to identifying biobased technologies, challenges, and opportunities. Holland, & Shapira, P., 7 Feb 2024, (E-pub ahead of print) In: Engineering Biology.
Building a Bottom-Up Bioeconomy. Shapira, Matthews, Cizauskas, Aurand, Friedman, Layton, Maxon, Palmer, & Stamford, (2022) In: Issues in Science and Technology. 38, 3, p. 78-83.
HARNESSING UK STRENGTHS IN BIOMANUFACTURING
PHARMACEUTICALS VALUE-ADDED CHEMICALS
ENGINEERING MATERIALS
ADVANCED SYNTHETIC FUELS
Technical Platform Themes support sector-based product foci of Pharmaceuticals; Value-Added Chemicals; Engineering Materials; Advanced Synthetic Fuels.
PHARMACEUTICALS:
Biomanufacturing approaches, and the use of biocatalysts is widely embedded in the pharmaceutical sector. This theme further develops and optimises novel enzyme catalysts and the SYNBIOCHEM pipeline to access diverse API targets. Work has included extension of microbial biosynthesis of key intermediates in the alkaloid pathways towards morphinan targets, and rapid prototyping of shikimate pathway ‘gate-keeper’ molecules for flavanone targets.
INDUSTRY PROJECTS: Working with GSK to engineer and optimise imine reductase enzymes in the synthesis of pharmaceuticals and APIs, and with Phytome for the biomanufacture of plant-derived active ingredients.
ADVANCED SYNTHETIC FUELS:
To develop renewable production routes that will allow us to transition away from a dependence on fuels derived from fossil sources (petrochemicals). Harnessing biocatalyst design and strain engineering for microbial cell factories able to convert waste biogenic carbon and CO2 into valuable fuels. Early work focused on the microbial production of BioLPG through to biosynthetic pathways for the production of aviation fuel precursors such as Linalool.
HIGHLIGHT PUBLICATION: Park, Toogood, Chen, Scrutton (2022). Co-production of biofuel, bioplastics and biochemicals during extended fermentation of Halomonas bluephagenesis. Microbial Biotech. 14158.
INDUSTRY PARTNER PROJECTS: Partnering for the biomanufacture of precursors for advanced synthetic fuels (Shell, C3 BIOTECH) and industrial host engineering for chemicals and fuels (bp, C3 BIOTECH).
VALUE-ADDED CHEMICALS:
To access alternatives to petrochemical-based manufacturing routes in lower value, higher volume chemical sectors require different technical and economic challenges to be surmounted. Finding more sustainable ways to produce chemicals needed for everyday life will be important in our bid to meet the global challenges and net-zero targets. One such project has seen high titre bio-styrene production through whole-cell cascade bio-transformations which overcomes the problems of product toxicity which limits yields seen with microbial production routes.
HIGHLIGHT PUBLICATION: High-titer Bio-Styrene Production Afforded by Whole-cell Cascade biotransformation (2023) Messiha, Scrutton & Leys, ChemCatChem, 15, e202201102 DOI: 10.1002/cctc.202201102
EPSRC FUNDED PROSPERITY PARTNERSHIP AWARD WITH SHELL:
The Future BRH were delighted to see the new Prosperity Partnership collaboration with Shell. The 5-year Industry/UKRI award (>£9M) aims to find new sustainable routes to manufacturing commodity chemicals and de-risking processes for industry.
The project builds on a long-standing relationship with Shell on the discovery and characterisation of new enzymes and some of the work undertaken by Hub researchers for sustainable commodity chemical production.
ENGINEERING MATERIALS:
Development of sustainable, bio-based materials from biology as alternatives to petrochemical-derived products, and recycling methods to transition towards a circular bio-based materials approach.
Future BRH has extended earlier collaborations to develop advanced materials with enhanced properties (e.g., tuneable optical properties, high-tensile strength, and novel polymers and composites based on aramid fibres) to look at functional materials (e.g., biosynthetic fibres and bio-adhesives) for a variety of uses that include protection and aerospace.
Future BRH is working to deliver scaled production of key monomers for polymerisation, extending the SYNBIOCHEM centre work towards bio-sustainable production.
This theme has been extended to wider materials applications, including end-of-life recycling (from discussions with our industry partners and aims for a circular economy) and the development of biocomposites (see below) which contributed to the formation of a spin-out company (Deakin Bio-hybrid Materials Ltd) and attraction of significant media attention.
TAKING BUILDING MATERIALS TO ANOTHER DIMENSION IS STARCRETE:
Robust and affordable technology capabilities are needed before a sustained human presence on the lunar and Martian surfaces can be established. A key challenge will be the production of high-strength structural materials from in situ resources to provide spacious habitats with adequate radiation shielding. Ideally, the production of such materials will be achieved through relatively simple, low-energy processes that support other critical systems.
In this work, we demonstrated the use of ordinary starch as a binder for simulated extraterrestrial regolith to produce a high strength biocomposite material, termed StarCrete. With this technique, surplus starch produced as food for inhabitants could be used for construction, integrating two critical systems, and significantly simplifying the architecture needed to sustain early extraterrestrial colonies. After optimisation, lunar and Martian StarCrete achieved compressive strengths of 91.7 and 72.0 MPa, respectively, which is well within the domain of high-strength concrete (>42 MPa).
PUBLICITY:
• The Engineer - StarCrete offers high-strength solution for off-world buildings
• Scientists invent ‘cosmic concrete’ to build houses on Mars | The Independent
• Scientists create super-strength ‘cosmic concrete’ for building on Mars (telegraph.co.uk)
• “Cosmic Concrete” Made From Extra-Terrestrial Dust Is Twice As Strong as Regular Concrete (scitechdaily.com)
• How Close Are We to Calling the Red Planet Home? (youtube.com)
Aled Roberts in interview with BBC Click discussing StarCrete
WIDER ENGAGEMENT
OUTREACH AND ENGAGEMENT
As a member of the Bio Industries Association (BIA) Engineering Biology Advisory Committee, Ros Le Feuvre represented Future BRH at the BIA fringe event at the Conservative party conference joining the discussion around ‘Can biotechnology save the world’. The Science Minister George Freeman spoke boldly about replacing fossil fuel-based supply chains, whilst the panel members highlighted the importance of the UK bioeconomy and the barriers that remain, including the need for agile regulation.
Ros was pleased to be invited onto the panel for the BIA fringe event at the Labour party conference with the opportunity to highlight the MIB, engineering biology, benefits of interdisciplinary research and the need for continued investment in this area. Ros was joined by Philip Shapira and Adam McCarthy from the Manchester Institute of Innovation Research (Alliance Manchester Business School) bringing their expertise in Responsible Research and Innovation in relation to Emerging technologies.
Members of the MIB, RRI team and policy@manchester, also contributed to the Engineering biology call for evidence which provided an opportunity to highlight key areas of priority to support engineering biology in the UK going forward. The Prime Minister’s Council for Science and Technology: Engineering Biology: opportunities for the UK economy and national goals also is an interesting read. (Weblink)
OUTREACH EVENTS
TRAINING THE FUTURE GENERATION: The Future BRH team welcomed a class of T-level students from Manchester College with a tour of facilities and an opportunity to discuss life and career as scientists, another group returned for a tour of the analytical suites and 4 students joined the Future BRH on work placements in June.
ENGAGING AT SCIENCE FESTIVALS: Engagement with schools and wider public included hosting a stand at the Malvern Festival of Innovation Family Day Event on 7 October 2023 and British Science Week event on 11-12 March 2024. The Future BRH stall exhibited 9 different activities based around the concepts of ‘Bio-based manufacturing’ and ‘Cell as Factory’, exploring topics such as microbes, bio-based chemicals, biosensors, and genetic coding. One of the secondary school science teachers was inspired to update his knowledge of latest developments in biotechnology. Other comments we had were - “I learned loads about bacteria”, “It was much more interactive than I thought” and “Science is everywhere”.
IMPACTING THE REGIONAL ECOSYSTEM: On 9 January 2024, Future BRH invited a local farmer as part of our initiative to gain valuable insights from wider public in the field. Michael Lewis a farmer, renewable energy enthusiast as well as a Beekeeper shared his valuable perspectives on our research, discussed challenges he encounters and explored how our research might positively impact his life.
WIDER ENGAGEMENT
NORTH WEST WORKSHOPS
Future BRH also participated in three North West focused foresight workshops funded through Manchester University to explore pathways to sustainable biomanufacturing, future feedstocks, and skills and training needs. Attended by manufacturers, end-users, policymakers, trade associations, researchers, and academic experts these sessions were coordinated by an intern Ling-Li Boon, Neil Dixon, and Philip Shapira. New funding for a North West Industrial Biotechology Innovation Catalyst (EPSRC) will bring together the community through place-based impact acceleration initiatives.
PARTICIPATING AT OTHER OUTREACH EVENTS
"Pint of Science" is a worldwide science festival bringing scientific talks aimed at a general audience to pubs and cafes. A double-act on ‘Engineering vs Biology in Biomanufacturing’ presented a lightly comic exchange between Ms Gabriele Kalantaite (PhD student) and Dr Matthew Russell (Future BRH Fellow) debating whether biological or engineering approaches are most critical to developing biomanufacturing process before concluding both must work together. Along the way they described opportunities and challenges associated with biotech. There was laughter in interest from the audience and lots of great questions.
Future BRH members also attended various other events such as Para-lab report art-science showcase (Stall), NWBI 10-year-Anniversary celebration (Speech), Futureproof your Planet lecture (Online talk to schoolchildren), Materials and Machine Learning Meetup (In-person meetup and discussion with peers).
APPRENTICE: JENI KONGOLA
During my ongoing laboratorial technician degree apprenticeship in Bioscience, which started in September 2022, I commenced my placement here at the MIB in March 2023. Originally, I was assigned to the Future BRH to learn lab technician skills under Viranga Tilakaratna’s supervision, however alongside that, I was offered a great opportunity to engage in research with Dr Hanan Messiha. This involved gaining knowledge in protein purification, protein quantification such as Bradford Assay, data analysis, etc. Beyond my primary responsibilities, I actively participated in outreach in Malvern and Manchester Science Museum to show and teach children and teenagers some science. Moreover, I have shared insights of my unique degree apprenticeship journey to T-Levels college students from Manchester College, offering guidance and advice on alternative pathways to obtaining a degree. "My placement at MIB has not only enriched my technical skills but also enriched my scientific skills and all wouldn’t be possible without FBRH group."
MANAGEMENT TEAM
PROFESSOR NIGEL SCRUTTON
FUTURE BRH DIRECTOR, THE UNIVERSITY OF MANCHESTER
Nigel is Professor of Enzymology and Biophysical Chemistry at The University of Manchester. He is internationally recognised as a leader in the fields of enzyme engineering, structure and mechanisms, and biomanufacturing using synthetic biology and biocatalytic approaches.
DR YVONNE ARMITAGE
CENTRE FOR PROCESS INNOVATION (CPI)
Yvonne is Principal Strategic Programme Manager at CPI. She has significant experience in bioprocesses having worked for 20 years across a range of organisations including Ciba Specialty Chemicals, BASF, Ashland Specialities, Innovate UK and Sheffield Hallam University.
PROFESSOR PERDITA BARRAN
THE UNIVERSITY OF MANCHESTER
Perdita is Professor of Mass Spectrometry (MS) and Director of the Michael Barber Centre for Collaborative MS. She has considerable experience in novel MS approaches for chemical and biological problems, and HTP MS screening for biocatalyst discovery programmes.
LISA BEATTIE
FUTURE BRH SENIOR PROJECT ADMINISTRATOR, THE UNIVERSITY OF MANCHESTER
Lisa provides a pivotal role in the overall administration of the Future BRH and provides high level project support. She has previous experience of working on a number of multi-partner projects across a range of areas including biotechnology, materials science and public health.
DR MARK BUSTARD
IBIOIC
Mark is CEO at IBioIC and is responsible for its strategy and delivery of activities to grow the UK bioeconomy. IBioIC’s role is to engage, collaborate with and support large corporates, SMEs, academia and Government to accelerate and de-risk commercialisation, and to bring new biotechnology processes and products to market.
PROFESSOR ALEX CONRADIE
UNIVERSITY COLLEGE LONDON
Alex is Professor in Sustainable Bioprocess Engineering at University College London. He specialises in upstream processing, where he has spearheaded the establishment of gas fermentation technology and systems biology capabilities. His expertise extends to downstream processing, where he has commercialised continuous adsorption and crystallisation unit operations.
DR
SEBASTIAN COSGROVE
KEELE UNIVERSITY
Sebastian is a lecturer in organic chemistry at Keele University. An alumni of the Future BRH, he has since established his own group which is interested in the application of enzyme immobilisation and continuous flow biocatalysis towards the improvement of chemical and bioprocesses.
PROFESSOR DANIELA DELNERI
UNIVERSITY OF MANCHESTER
Daniela is a Professor of Evolutionary Genomics at the University of Manchester, with thirty years’ worth of experience in yeast genetics and functional genomics. She focusses on understanding the interplay between genes and environment.
PROFESSOR PAUL FREEMONT
IMPERIAL COLLEGE LONDON
Paul is Co-Director of the UK Innovation and Knowledge Centre (IKC) for Synthetic Biology SynbiCITE at Imperial College London. He has expertise in the development of Synthetic Biology platforms for healthcare and manufacturing.
PROFESSOR ANTHONY GREEN
THE UNIVERSITY OF MANCHESTER
Anthony is a lecturer in organic and biological chemistry at The University of Manchester. He leads a multidisciplinary research team with expertise in biocatalysis, directed evolution, enzyme design, organic synthesis and genetic code expansion.
DR BOB HOLT
CENTRE FOR PROCESS INNOVATION (CPI)
Bob is Chief Technologist for the Biotechnology business unit of CPI. During his industrial career with global pharmaceutical and contract manufacturing companies he has worked at the interface of biology and synthetic chemistry with a particular focus on cost-effective asymmetric synthesis.
PROFESSOR RICHARD KITNEY
IMPERIAL COLLEGE LONDON
Richard is Professor of Biomedical Systems Engineering and Co-Director/Co-Founder of the Centre for Synthetic Biology and Innovation at Imperial College London. He has published over 300 papers on synthetic biology, mathematical modelling and biomedical information systems.
DR ROSALIND LE FEUVRE
FUTURE BRH DIRECTOR OF OPERATIONS, THE UNIVERSITY OF MANCHESTER
Ros is responsible for the operational and strategic management of the Hub. She has significant experience coordinating large collaborative research programmes, was the Director of Operations for the SYNBIOCHEM Centre, and provides strategic research management to the MIB.
PROFESSOR GARY LYE
UNIVERSITY COLLEGE LONDON
Gary is Head of the UCL Department of Biochemical Engineering, and has over 20 years of experience working on the design and scale-up of biocatalytic processes involving both enzymatic and fermentative bioconversions.
DR MARCO MARQUES
UNIVERSITY COLLEGE LONDON
Marco is a Lecturer in the UCL Department of Biochemical Engineering. His main focus is on Industrial Biotechnology and specifically Sustainable Bioreaction Engineering principles to synthesise value-added chemicals and pharmaceuticals.
PROFESSOR PHILIP SHAPIRA
THE UNIVERSITY OF MANCHESTER
Philip is Professor of Innovation Management and Policy at the Manchester Institute for Innovation Research. He is internationally recognised for research, engagement and policy leadership in science and technology, innovation management, and responsible innovation.
Pamila is responsible for delivering a cohesive translation strategy for the Future BRH team and plays a crucial role in driving the strategic development, management and delivery of engagement activities, building interdisciplinary relationships both across industry and academia.
PROFESSOR NICOLAS SZITA
UNIVERSITY COLLEGE LONDON
Nicolas leads the Bioprocess Microfluidics Group at UCL and has expertise in microfluidic and continuous flow reactor technologies. He established a unique bioprocess microfluidics lab which has pioneered rapid prototyping techniques for microfluidic bioreactor technologies.
PROFESSOR ERIKO TAKANO
THE UNIVERSITY OF MANCHESTER
Eriko is Professor of Synthetic Biology at The University of Manchester. She is internationally leading in sythentic biology of antibiotic production, with expertise in engineering secondary metabolite biosynthesis pathways and industrially relevant organisms.
PROFESSOR CONSTANTINOS THEODOROPOULOS
THE UNIVERSITY OF MANCHESTER
Kostas is Professor of Chemical and Biochemical Systems Engineering at The University of Manchester. He has expertise in bioprocess synthesis, design and scale-up. He combines innovative experiments with multi-scale models of complex chemical/biochemical processes.
PROFESSOR NICHOLAS TURNER
UK CATALYSIS HUB
Nick leads the Biocatalysis and Biotransformations theme at the UK Catalysis Hub. He is an expert in the use of enzymes as biocatalysts for organic synthesis and biocatalytic manufacture, and is at the forefront of work on directed evolution of enzymes as applied biocatalysts.
KRIS WADROP
CENTRE FOR PROCESS INNOVATION (CPI)
Kris is General Manager - Commercial Operations at CPI. He is an experienced chemical engineer and Fellow of the IChemE, and has extensive experience in designing and managing chemical plants to complement his expertise in biorefining.
DR JAMES WINTERBURN
UNIVERSITY OF MANCHESTER
James is a Reader in Chemical Engineering with interests in industrial biotechnology, fermentation process development and the efficient production and separation of bio-based products. He is Co-Founder and Technical Director of Holiferm Ltd, which commercialises economically competitive biosurfactant producing fermentation technology at scale.
DR LOUISE WOODS
FUTURE BRH PROJECT MANAGER, THE UNIVERSITY OF MANCHESTER
Louise provides professional management for all aspects of the Future BRH. She has significant experience of project managing research projects from a wide range of funders, and also has a background in research support across the biotechnology field.
DR MOHAMED AMER
RESEARCH FELLOW
Mohamed received his BSc and MSc degrees in Biochemistry from Ain Shams University (Egypt) followed by a PhD in Chemistry from the University of Manchester. Mohamed is an accomplished synthetic biologist with a wealth of transferable skills acquired in both academic and industrial sectors.
DR ALEC BANNER
RESEARCH ASSOCIATE
Alec completed his MPhil (2018) and PhD in Chemistry (2023), from the University of Manchester. Within the Future BRH, Alec is developing novel strains for increasing metabolic substrate availability and helping to run the DoE and fermentation scale-up facilities.
DR KAOUTHAR ELJOUNAIDI
RESEARCH FELLOW
Kaouthar completed her PhD in Biochemistry from the University of Turin (Italy). She then worked as a postdoctoral research associate at the University of York. Her current projects in the Future BRH are focussed on developing biomanufacturing platforms for high value terpenoids and alkaloids.
DR MATTHEW FAULKNER
RESEARCH FELLOW
Matthew received his PhD from the University of Liverpool (UK) in 2018. Within Future BRH he is developing novel routes to biological carbon capture utilisation and storage using photosynthetic bacteria.
DR AZARMIDOKHT GHOLAMIPOUR-SHIRAZI
RESEARCH FELLOW
Azar completed her undergraduate and Masters qualifications in Chemical Engineering, followed by her PhD in organic and macromolecular chemistry at the University of Lille, France. Azar’s expertise spans a broad range of topics in chemical engineering and chemistry.
DR ELLIE GOULDING
RESEARCH ASSOCIATE
Ellie graduated from the University of Liverpool with a MChem degree in Chemistry in 2019, followed by a PhD focussing on biocatalysis in 2024. Within the Future BRH, Ellie is working on the engineering of halophilic production strains for biomanufacturing valuable products from waste feedstocks.
DR ERIK HANKO
RESEARCH FELLOW
Erik completed his PhD in Molecular Microbiology at the University of Nottingham (2020) then joined the Manchester Institute of Biotechnology as a Research Associate. One of Erik’s key interests lies in the design and engineering of small-molecule biosensors for facilitating high-throughput screening of microbial cell factories.
DR ELAHE HOJAJI
RESEARCH FELLOW
Elahe completed her PhD in Chemical and Energy Engineering at London South Bank University, then worked at the University of Surrey on the atomic-scale modelling of cathode of Lithium Ion Batteries. She joined the Future BRH to model Halomonas fermentation and then implement the proper control and monitoring platforms.
DR CHATCHAI KESORNPUN
RESEARCH FELLOW
Chatchai obtained his PhD in Chemical Biology from the Chulabhorn Royal Academy (Thailand). Within Future BRH, Chatchai is focused on microbial fermentation at lab scale with a view to scale up and sustainable process engineering for biomanufacturing.
DR HANAN MESSIHA
RESEARCH FELLOW
Hanan obtained her BSc in Pharmaceutical Sciences, followed by an MSc and PhD in Biochemistry. Within the Future BRH, her role involves the development of robust sustainable bio-routes to biomaterials, biofuel, key intermediates and chemicals for various industrial applications.
DR ALED ROBERTS
RESEARCH FELLOW
Aled received a PhD in Materials Chemistry jointly at the University of Liverpool and at the Institute of Materials Research and Engineering (IMRE) in Singapore. He has a broad academic background spanning chemistry, materials engineering and synthetic biology.
DR CHRIS ROBINSON
RESEARCH FELLOW
Chris studied Biochemistry and Molecular Biology in Manchester before earning his PhD at the Paterson Institute for Cancer Research. Within the Future BRH, his current research involves the construction of biosynthetic pathways and engineering microbial host strains for the production of diverse small molecule targets.
DR MATTHEW RUSSELL
RESEARCH FELLOW
Matthew is an analytical biochemist specialising in quantitative protein mass spectrometry. He has a PhD in Biochemistry from the University of Cambridge. Within the Future BRH Matthew is focused on analytical methods to quantify enzyme expression in host strains.
DR REEM SWIDAH
RESEARCH ASSOCIATE
Reem obtained her PhD in Biotechnology from the University of Manchester, specialising in biobutanol in Saccharomyces cerevisiae. She joined the Future BRH to work on engineering non-conventional yeast to produce different products. Reem received the prestigious L’Oréal UNESCO Award for Women in Science 2024.
VIRANGA TILAKARATNA
SENIOR RESEARCH TECHNICIAN
Viranga obtained a Masters in Biotechnology from the University of Peradeniya (Sri Lanka). She supports the overall delivery of the Future BRH research programme and provides coordination of laboratory health and safety and procurement for the research team.
DR HELEN TOOGOOD
SENIOR EXPERIMENTAL OFFICER
Helen obtained her PhD degree in the biochemistry of extremophile enzymes at the University of Waikato (New Zealand). Her main research focus is the development of commercially viable synthetic biology routes to biofuels and other biochemicals using microorganisms as ‘microbial chassis.’
DR FEDERICO VISINONI
RESEARCH ASSOCIATE
Federico received his BSc and MSc degrees in Industrial Biotechnology from the University of Milan-Bicocca (Italy), then PhD from the University of Manchester. He is a fermentation scientist with a strong background in genetics and molecular biology.
DR JOSHUA WHITEHEAD
RESEARCH ASSOCIATE
Josh obtained a BSc in Chemistry from the University of Manchester (2019), followed by an MRes in Systems and Synthetic Biology from Imperial College London. He obtained his PhD at the University of Manchester (2023). Josh’s research interests are focused on enzyme engineering and characterisation, and the chemistry of catalysis.
Research Project: ‘A biosynthetic platform for plant-derived therapeutics: Enzymatic production of novel flavonoids as potential anti-inflammatory drug candidates’
Research Project: ‘Modelling concerted microbial metabolic activities to mimic multicellular behaviour and its applications in biotechnology and biomanufacturing’
Research Project: ‘Towards biofilm reactors for flow biocatalysis: investigating the productivity of biofilms for commodity chemical production in a microfluidic scale-down model’
Research Project: ‘Monitoring and Control of Continuous Halomonas Fermentations for Sustainable Production of Commodity Chemicals from Renewable Feedstocks’
THE TEAM
FORMER TEAM MEMBERS
DR IAN ARCHER
THE INDUSTRIAL BIOTECHNOLOGY INNOVATION CENTRE (APRIL 2019 TO AUGUST 2023)
Ian is Technical Director of IBiolC tasked with shaping IBioIC’s strategy and implementing their business plan. He is the technical link with IBioIC’s industrial membership and has a strong background in synthetic chemistry and process development.
DR ADOKIYE BEREPIKI
RESEARCH FELLOW (SEPTEMBER 2019 TO MARCH 2021)
Adokiye is a strain engineer who has worked on a range of projects during six years of postdoctoral research, specialising in metabolic engineering, synthetic biology, recombinant protein production and fermentation.
DR MARIJAN BAJIĆ
RESEARCH FELLOW (DECEMBER 2019 TO DECEMBER 2023)
Marijan received his PhD in Biotechnology from the University of Ljubljana (Slovenia) in 2017. His research in the Future BRH is focused on the development and characterisation of microreactors for continuous enzymatic synthesis.
DR YONG CHEN
RESEARCH FELLOW (MAY 2020 TO DECEMBER 2021)
Yong received a PhD in Biology from Tsinghua University (China) focused on pathway construction and mechanical properties of biodegradable polymers. His research interests are in synthetic pathway design, automation high throughput screening, and metabolic flux control.
DR TOBIAS HEDISON
RESEARCH FELLOW (SEPTEMBER 2019 TO MARCH 2023)
Tobias was awarded a PhD in Biophysical Chemistry from The University of Manchester in 2016. Within the Future BRH he is is focused on the development of industrial biocatalysts and high throughput assays to study enzyme turnover.
DR NICOLE LEFERINK
RESEARCH FELLOW (AUGUST 2019 TO MAY 2024)
Nicole obtained her PhD degree from Wageningen University in the Netherlands. She has experience in enzyme discovery, characterisation, and engineering, high-throughput screening, laboratory automation, and biomanufacturing using synthetic biology.
THE TEAM
FORMER TEAM MEMBERS
DR KIRK MALONE
FUTURE BRH DIRECTOR OF COMMERCIALISATION (APRIL 2019 TO MAY 2023)
Kirk has extensive experience in university business engagement, with a track record of securing collaborative R&D funding (over £66M). Within Future BRH his focus is to deliver impact through translational activities and co-creation of programmes with industry.
DR CLARE MEGARITY
RESEARCH FELLOW (OCTOBER 2021 TO JUNE 2022)
Clare was awarded a PhD from Queen’s University Belfast in 2014 where she studied the molecular basis of negative cooperativity in oxidoreductase flavoenzymes. As a Future BRH Research Fellow, Clare is continuing her work with the Electrochemical Leaf for fundamental enzyme cascade research.
DR
AISLING
NÍ CHEALLAIGH
RESEARCH FELLOW (NOVEMBER 2021 TO AUGUST 2022)
Aisling is a synthetic organic chemist and well versed in process development and scale up of biologically active modules. Her research focuses on the incorporation of enzymatic processes into the production of active pharmaceutical ingredients and value added chemicals.
DR KARL PAYNE
RESEARCH FELLOW (JULY 2019 TO JUNE 2021)
Karl received a PhD in Biochemistry from the University of Leeds. He has expertise in enzymes that play a role in bioremediation of pollutants or production of hydrocarbons for fuels/plastics. His research focuses on structural enzymology, protein engineering and synthetic biology.
DR ITZIAR PENAFIEL
RESEARCH FELLOW (JULY 2019 TO JUNE 2021)
Itziar received her PhD in Organic Chemistry from the University of Alicante (Spain) in 2012. She is interested in the development of industrially interesting biotransformations under continuous flow, including multi-enzymatic cascades and enzyme immobilisation.
DR MAURO RINALDI
RESEARCH FELLOW (OCTOBER 2021 TO JULY 2023)
Mauro received his PhD in Biochemistry and Cell Biology from Rice University, Houston TX. His current research focus is metabolic engineering through directed evolution and improving tolerance to intermediate and end-product toxicity in production hosts through synthetic biology.
THE TEAM
FORMER TEAM MEMBERS
DR WILLIAM ROWE
SENIOR EXPERIMENTAL OFFICER (MAY 2020 TO MAY 2021)
William received his PhD in biocolloid science in 2002 and then worked at Unilever R&D in the laundry research team. Since retraining in bioinformatics he has worked on a variety of projects across the University of Manchester and within Future BRH analysing large omics datasets.
DR CHENHAO SUN
RESEARCH FELLOW (APRIL 2020 TO SEPTEMBER 2021)
Chenhao Sun received his MEng and PhD in Chemical Engineering with Biotechnology from The University of Manchester in 2017. He specialises in downstream process design and techno-economic analysis for early-stage fermentation processes.
DR JOSEPH WEBB
RESEARCH FELLOW (JUNE 2021 TO APRIL 2023)
Joe completed his PhD in biotechnology at the University of Nottingham. Joe’s projects have focused on metabolic engineering of microbial chassis to produce industrially relevant chemicals at high titre. Within Future BRH he is developing microbial strains for the bioproduction of various chemicals.
DR JOHN WHITTALL
RESEARCH FELLOW (JULY 2020 TO JUNE 2022)
John has over 40 years of experience as an industrial research chemist working for several different chemical companies. As such he has the experience of taking several products from initial research concept to the research bench and into industrial application in diverse areas.
DR JONATHAN WILKES
RESEARCH FELLOW (JULY 2020 TO MARCH 2023)
Jonathan received his PhD under the supervision of Prof Nigel Scrutton, in the Manchester Institute of Biotechnology. Jonathan’s research interests include metabolic engineering and the application of ‘Design of Experiments’ for the development of microbial cell factories.
DR YIHENG YANG
RESEARCH FELLOW (JANUARY 2022 TO JANUARY 2023)
Yiheng received his PhD in Biochemical Engineering from the University College London. Within Future BRH Yiheng is working on the development of transferable models for monitoring, control and optimization of Halomonas continuous fermentation.
