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Contributors
S. Ahmed Savitribai Phule Pune University, Pune, Maharashtra, India
F.C.T. Allnutt BrioBiotech LLC, Glenelg, MD, United States
N. Arul Manikandan Department of Chemical Engineering, Indian Institute Technology Guwahati, Guwahati, Assam, India
M. Ayadi National Engineering School of Tunis, Tunis, Tunisia
B. Bharathiraja Vel Tech High Tech Dr. Rangarajan Dr. Sakunthala Engineering College, Chennai, Tamil Nadu, India
J.F. Blais Institut national de la recherche scientifique Centre - Eau Terre Environnement (INRSETE), Quebec, Canada
S.K. Brar Institut national de la recherche scientifique Centre - Eau Terre Environnement (INRSETE), Quebec, Canada
E. Chaabouni Institut national de la recherche scientifique Centre - Eau Terre Environnement (INRS-ETE), Quebec, Canada
M. Chakrabortty Assam Engineering College, Guwahati, Assam, India
M. Chakravarthy Vel Tech High Tech Dr. Rangarajan Dr. Sakunthala Engineering College, Chennai, Tamil Nadu, India
R. Chidambaram VIT University, Vellore, Tamil Nadu, India
B.K. Das Gauhati University, Guwahati, Assam, India
N. Dasgupta VIT University, Vellore, Tamil Nadu, India
R.K. Das Institut national de la recherche scientifique Centre - Eau Terre Environnement (INRSETE), Quebec, Canada
A. Daverey Doon University, Dehradun, Uttarakhand, India
K. Dutta National Institute of Technology Rourkela, Rourkela, Orissa, India
A. Ghosh Indian Institute of Technology Guwahati, Guwahati, Assam, India
K.P. Gopinath SSN College of Engineering, Chennai, India
R. Goswami Rajiv Gandhi University of Knowledge Technologies, Nuzvid, Andhra Pradesh, India
B.Z. Haznedaroglu Yale University, New Haven, CT, United States; Bogazici University, Istanbul, Turkey
K. Hegde Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, India; Institut national de la recherche scientifique Centre - Eau Terre Environnement (INRS-ETE), Quebec, Canada
J. Jayamuthunagai Anna University, Chennai, Tamil Nadu, India
P. Kalita The Energy and Resources Institute, New Delhi, India
A. Kumar National Institute of Technology Raipur, Raipur, Chhattisgarh, India
R. Kumar VIT University, Vellore, Tamil Nadu, India
L. Lonappan Institut national de la recherche scientifique Centre - Eau Terre Environnement (INRS-ETE), Quebec, Canada
B. Mahanty INHA University, Incheon, Korea
D.C. Maiti Vidyasagar University, West Bengal, India
S. Maiti Institut national de la recherche scientifique Centre - Eau Terre Environnement (INRSETE), Quebec, Canada
C. Marques Institut national de la recherche scientifique Centre - Eau Terre Environnement (INRS-ETE), Quebec, Canada; Ponta Grossa State University, Ponta Grossa/PR, Brazil
N. Meyyappan Sri Venkateswara College of Engineering, Sriperumbudur, Chennai, Tamil Nadu, India
V.K. Mishra Rajiv Gandhi University of Knowledge Technologies, Nuzvid, Andhra Pradesh, India
N. Mohan Indian Institute of Technology Guwahati, Guwahati, Assam, India
L. Nivedhitha SSN College of Engineering, Chennai, India
V.L. Pachapur Institut national de la recherche scientifique Centre - Eau Terre Environnement (INRS-ETE), Quebec, Canada
K. Pakshirajan Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, India
R. Parthiban Sri Sivasubramaniya Nadar College of Engineering, Chennai, Tamil Nadu, India
J. Peccia Yale University, New Haven, CT, United States
A. Prabhu Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, India
R. Praveen Kumar Arunai Engineering College, Tiruvannamalai, Tamil Nadu, India
G. Pugazhenthi Department of Chemical Engineering, Indian Institute of Technology Guwahati, Guwahati, Assam, India
R. Pulicharla Institut national de la recherche scientifique Centre - Eau Terre Environnement (INRS-ETE), Quebec, Canada
R. Ranjith Kumar Vel Tech High Tech Dr. Rangarajan Dr. Sakunthala Engineering College, Chennai, Tamil Nadu, India
D. Reeves Weill Cornell Graduate School of Medical Sciences, New York, NY, United States
H. Rismani-Yazdi Yale University, New Haven, CT, United States; Novozymes North America Inc., Franklinton, NC, United States
T. Rouissi Institut national de la recherche scientifique Centre - Eau Terre Environnement (INRSETE), Quebec, Canada
T.S. Saai Anugraha Sri Venkateswara College of Engineering, Sriperumbudur, Chennai, Tamil Nadu, India
A.R. Sankaranarayanan SSN College of Engineering, Chennai, India
M. Sara Institut national de la recherche scientifique Centre - Eau Terre Environnement (INRSETE), Quebec, Canada
S.J. Sarma Institut national de la recherche scientifique Centre - Eau Terre Environnement (INRS-ETE), Quebec, Canada
S. Sen VIT University, Vellore, Tamil Nadu, India
S. Sivaprakasam Indian Institute of Technology Guwahati, Guwahati, Assam, India
C.R. Soccol Federal University of Paraná, Curitiba, Brazil
S. Sulochana Sri Venkateswara College of Engineering, Sriperumbudur, Chennai, Tamil Nadu, India
I.S. Sundari VIT University, Vellore, Tamil Nadu, India
D. Swaminathan Sri Venkateswara College of Engineering, Sriperumbudur, Chennai, Tamil Nadu, India
T. Swaminathan Sri Venkateswara College of Engineering, Sriperumbudur, Chennai, Tamil Nadu, India
R. Tarek Institut national de la recherche scientifique Centre - Eau Terre Environnement (INRSETE), Quebec, Canada
J.M.R. Tingirikari Federal University of CearaFortaleza, Benfica, Fortaleza-CE, Brazil
V. Venkata Dasu Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam, India
M. Verma CO2 Solutions Inc., Quebec City, QC, Canada
R. Vinoth Kumar Department of Chemical Engineering, Indian Institute of Technology Guwahati, Guwahati, Assam, India
V.K. Yata Dr. B.R. Ambedkar National Institute of Technology Jalandhar, Jalandhar, Punjab, India
Preface
Platform chemicals are a diverse group of chemicals that can be used as the building blocks/structurally close starting materials for the production of different valuable chemicals, including fuel, pharmaceutically important compounds, or industrial chemicals. At present, the platform chemical market is mostly dominated by petroleum-based platform chemicals. However, owing to the depletion of petroleum-based raw materials as well as environmental pollution due to the extensive use of such materials, the concept of renewable feedstock-based platform chemical refinery is gaining attention. Although the concept has been independently discussed by various researchers, a repository of detailed technical know-how and possible environmental and marketrelated concerns is rare.
Biorefinery is a concept where more than one product can be produced by maximum utilization of the same feedstock. The actual picture at present encompasses the use of renewable feedstock for the production of only one or two major products. The products simultaneously produced in lower quantities or the waste generated during the process, which could potentially be used as raw materials for the production of certain other valuable products, are largely ignored. The biorefinery approach is still marred by many bottlenecks: (1) nonexistent technology for the simultaneous production and recovery of more than one product, (2) scant information regarding the type and quantity of all by-products produced during a process, (3) limited association between chemical engineering and biotechnology,
(4) underrepresented statistics on the present and potential market of renewable platform chemicals, and (5) complete packaging of the approach in a streamlined manner. At this crux of few knowns and large unknowns, the purposes of this book are to gather contemporary knowledge on the subject, make a critical evaluation, and present it to the scientific community in a systematic manner.
The book has three distinct features. First, it completely covers all aspects of the subject and a basic introduction to the industry. It will be sufficient for a beginner to have an up-to-date overview of the concept. Further, biorefinery professionals will be introduced to recent advances of the technology. Likewise, possible bottlenecks of the technology have been brought to the focus of the research community involved in fundamental research for potential solutions. Second, the book presents a critical review of the platform chemical biorefinery concept. A critical analysis of the renewable platform chemical production processes has highlighted their benefits and, at the same time, their possible adverse effects on the environment and food security. Finally, in addition to discussing the engineering advancement in the field of renewable platform chemical production technology, there is an overview of the present and potential global market for the most common renewable platform chemicals. Thus the book will equip renewable chemical industries to explore new market opportunities.
The book will also be suitable as a reference book for different universities that have courses/research facilities on varied
subjects, such as chemical/biochemical engineering, industrial biotechnology, biochemistry, industrial microbiology, environmental biotechnology, environmental engineering, and fermentation technology. In addition to university students and scientists doing regular academic research, the book readership includes professional researchers and technical staff working in the industries dealing with industrial chemical manufacturing or industrial biotechnology. The concept of renewable platform chemicals is relatively
new in large developing nations, such as India, Brazil, South Africa, and China; however, they have a vast potential for developing platform chemical biorefineries in the coming years. This book can also serve as a technical guide worldwide to potential entrepreneurs keen to develop biorefinery.
V.L. Pachapur, S.J. Sarma, S.K. Brar, E. Chaabouni
Institut national de la recherche scientifique Centre - Eau Terre Environnement (INRS-ETE), Quebec, Canada
1.1 INTRODUCTION
Global petrochemical production of platform chemicals derived from fossil-based feedstocks (oil, coal, gas) is estimated to be around 330 million tons. The initial output is dominated by building blocks and converted into a staggering number of different fine and specialty chemicals with specific functions (Jong et al., 2012). The US Department of Energy listed out chemicals such as 3-Hydroxy-propionic (3-HP) acid and xylitol, to name just two, which are the potential building blocks for the future (Jong et al., 2012).
The chemical way of synthesizing these chemicals amplifies concerns over global warming, the depletion of fossil fuels, increased environmental pollution, and higher energy inputs ( Wee et al., 2004 ) in the presence of toxic catalysts and several treatment steps during production ( Pérez-Bibbins et al., 2013 ). Due to increases in oil prices, the population, and consumer demand for environmentally friendly products and the scarcity of nonrenewable resources ( Jong et al., 2012 ), the focus of interest has been on the microbial-based generation of chemical commodities from waste resources ( Cooksley et al., 2012 ).
The production of platform chemicals through biotechnological fermentation has gained significant attention because it is a better alternative to chemical synthesis, avoids depletion of petrochemical resources, and decreases environmental pollution by utilizing renewable biomass wastes (Wee et al., 2004). Under favorable market conditions, the production of chemicals from renewable resources can reach 113 million tons by 2050, which is 38% of the total organic chemical production. With biorenewable chemicals such as lactic acid and glycerin accounting for 79.2% of the market in 2010, the projected biorenewable chemicals market will be around 6.8 billion in 2015 (Jong et al., 2012).
The best method of biorenewable synthesis of chemicals is the fermentation process, which requires milder conditions of pressure and temperature, utilizing low-cost renewable resources such as industrial wastes, municipal waste, or sludge from treatment processes. Another benefit is the low costs of downstream with the production of lower amounts of byproducts (Pérez-Bibbins et al., 2013). A very important advantage of microbial fermentation is the production of optically pure compounds in comparison to chemical synthesis, resulting in racemic mixtures (Wang et al., 2010a).
The production of bio-based chemicals has focused on the use of pure or easily fermentable substrates to decrease the process economics; low-cost organic waste materials are considered to enhance productivity (Wang et al., 2010a,b). A further increase in production can be achieved by using engineered microorganisms, minimizing (Jiang et al., 2009b) the production of undesired by-products (Ye et al., 2013) and the use of neutralizing agents (Roa Engel et al., 2011) while improving the product recovery step (Wu et al., 2010) and increasing product purity (Misra et al., 2011). With these advantages the production of bio-based chemicals through fermentation is a cost-effective, efficient, less time-consuming, and environmental friendly procedure.
Thus the purpose of this chapter is to summarize the advances and future commercial importance of biomass-derived platform chemicals, including different organic acids and alcohols are presented across (Tables 1.1–1.4).
TABLE 1.1 Conversion Pathways, derivatives, and Potential Applications of Bio-based Organic Acids
Platform
Chemical Other Names Pathways
1 3-Hydroxypropionic acid
2 Lactic acid
3-Hydroxypropanoic acid (IUPAC)
3-Hydroxypropionic acid
Hydracrylic acid
Ethylene lactic acid
IUPAC 2-Hydroxypropanoic acid
Milk acid
Aerobic fermentation
3 Fumaric acid
IUPAC (E)-Butenedioic acid
trans-1,2-Ethylenedicarboxylic acid
2-Butenedioic acid
trans-butenedioic acid
Allomaleic acid
Boletic acid
Donitic acid
Lichenic acid
4 Butyric acid
IUPAC Butanoic acid
Butyric acid; 1-Propanecarboxylic acid;
Propanecarboxylic acid
Aerobic fermentation
Anaerobic fermentation
Derivatives or Derivative
Family
1,3 Propanediol
Acrylate family
Potential Applications
Sorona fiber
Contact lenses, diapers
Lactate ester
Polylactic acid (PLA)
Acrylic acid
1,2-Propanediol
Pyruvic acid
Aerobic fermentation
Chemical process
THF, BDO, GBL family
Pyrrolidinone family
Straight chain polymers
Branched polymers
Hygroscopic and emulsifying properties, solvents
Biodegradable plastic
Acrylate polymers, biochemical intermediate
Commodity chemical
Solvents, fibers
Green solvents, water-soluble polymers
Fibers
1,5,7-triazabicyclo[4.4.0] dec-5-ene (TBD)
References
Werpy et al. (2004)
Gao et al. (2012)
Werpy et al. (2004)
Anaerobic fermentation
R)-3-(Boc-amino)-4-(4bromophenyl)butyric acid
Cosmetics, pharmaceuticals, and as a “natural preservative” in the food industry
Zhang et al. (2009)
TABLE 1.2 Conversion Pathways, derivatives, and Potential Applications of Bio-based Alcohols
Platform
Chemical Other Names Pathways
1 Xylitol IUPAC (2R,4S)-Pentane1,2,3,4,5-pentol
1,2,3,4,5-Pentahydroxypentane; Xylite
2 Butanol
Butan-1-ol[1]
Butalcohol
Butanol
1-Butanol
Butyl alcohol
Butyl hydrate
Butylic alcohol
Butyralcohol
Butyric alcohol
Butyryl alcohol
Hydroxybutane
Propylcarbinol
Aerobic fermentation
Anaerobic fermentation
Enzymatic transformation
Derivatives or Derivative Family Potential Applications References
Xylaric and xylonic acids
Polyols (propylene and ethylene glycols), lactic acid
Xylitol, xylaric, xylonic polyesters and nylons
Antifreeze, unsaturated polyester resins (UPRs)
New polymer opportunities Werpy et al. (2004)
Anaerobic fermentation 2-Methyl-2-butanol, 2-butanol As alternative fuel Cooksley et al. (2012)
C. beijerinckii ATCC 10132 Glucose Batch fermentation
C. acetobutylicum Cassava bagasse hydrolysate Fibrous-bed bioreactor
C. acetobutylicum
Glucose in the presence of biodiesel as an extractant Fed-batch fermentation
Cheng et al. (2009)
Kamal et al. (2011)
Huang et al. (2011a)
Prakash et al. (2011)
Oh et al. (2013)
Sun and Liu (2012)
Cheng et al. (2012)
Isar and Rangaswamy (2012)
Lu et al. (2012)
Yen and Wang (2013)
1.2
COMMERCIALLY IMPORTANT PLATFORM CHEMICALS: ORGANIC ACIDS
Organic chemicals such as organic acids can be used to synthesize plastic materials and other products. To meet the increasing demand for organic chemicals, more efficient, costeffective, and environmentally friendly production methods are being developed, which utilize raw materials.
1.2.1 3-Hydroxy-propionic Acid
3-HP acid (also called 3-Hydroxypropanoic acid, hydracrylic acid, and ethylene lactic acid) is a three-carbon carboxylic acid that has an interesting industrial potential and stands third on the list of the top 12 platform chemicals in the United States. It contains two functional groups with different properties that make it a suitable precursor for many applications, ranging from synthesizing optical active substances to acting as a cross-linking agent for polymer, metal lubricants, and antistatic agents for textiles. It has been included in the top value-added chemicals among renewable biomass products, as listed by the US Department of Energy (Gokarn et al., 2007; Raj et al., 2008). In fact, 3-HP can serve as a precursor for a number of commodities and specialties, such as acrylamide, 1,3-propanediol, acrylic acid, and methyl acrylate. Moreover, 3-HP can also be used to synthesize chemical intermediates such as malonic acid, propiolactone, and alcohol esters of 3-HP (Gokarn et al., 2007). Several chemical synthesis routes have been described to produce 3-HP, including oxidation from either 1,3-propanediol or 3-hydroxypropionaldehyde and hydration from acrylic acid. A global market opening at 3.63 million tons per year has been estimated for 3-HP (Raj et al., 2008). For commercial use 3-HP is produced by organic chemical synthesis, which is relatively expensive, and it is prohibited from being used for the production of monomers (Suthers and Cameron, 2005).
1.2.2 Lactic Acid
Lactic acid (2-hydroxypropionic acid) is a traditional chemical organic acid that is used as a natural preservative in many food products and widely used for specialized industrial applications (Maeda et al., 2009; Zhao et al., 2010; Taskin et al., 2012). It’s a raw material for 2,3-pentanedione, propanoic acid, acrylic acid, acetaldehyde, lactate ester, and as dilactide in chemical industries (Wee et al., 2004). Due to its properties such as optical activity, hydroxyl and carboxyl moieties are exploited for safe applications in the pharmaceutical, textile, and cosmetic industries (Wang et al., 2010a,b). For improved human health, many food products such as yogurt, Yakult, and bread contain lactic acid. Lactic acid is used as a feedstock for biodegradable polymers, oxygenated chemicals, plant growth regulators, environmentally friendly green solvents, and specialty commodity–chemical intermediates (Maeda et al., 2009). The global consumption of lactic acid is estimated to be around 130,000–150,000 metric tons annually and is expected to increase 7% per year until 2013 (Wee and Ryu, 2009; Djukic-Vukovic et al., 2012). The demand for lactic acid production is increasing continuously due to its extensive application as a precursor of polylactic acid, a promising biodegradable polymer (Wang et al., 2010a).
1.2.3 Fumaric Acid
Fumaric acid is a C4 unsaturated dicarboxylic acid that is widely used as a building block for a variety of chemicals and polymers. It is also used in the food, chemical, and pharmaceutical industries (Xu et al., 2010; Roa Engel et al., 2011). Fumaric acid is used in ruminal digesta to decrease methane formation and increase glucogenesis; it also increases milk yield in the agricultural industry (Wood et al., 2009). It serves as an important intermediate for esterification reactions and is identified as one of the top 12 building block chemicals by the US Department of Energy (Yu et al., 2012). It is used as an acidulant in foods, beverages, and industrial products, including lubricating oils, inks, and lacquers, and as a carboxylating agent for rubber. Fumaric acid is primarily produced through the catalytic oxidation of petrochemical hydrocarbons to maleic anhydride, followed by hydrolysis into maleic acid, and finally isomerization into fumaric acid. Due to increasing prices of petroleum oil and depleting fossil reserves, the bio-based production of fumaric acid has generated attention (Zhang et al., 2012).
1.2.4 Butyric Acid
Butyric acid, a four-chain short chain fatty acid, is an important specialty chemical with wide industrial applications in the chemical, foodstuff, and pharmaceutical industries. It is also used in manufacturing plastics, emulsifiers, disinfectants, and esters (Zhang et al., 2009; Song et al., 2010). It is used in the form of pure acid in food flavors, as additives for increasing fruit fragrance, and as aromatic compounds in perfumes. Its roles in health care as multiple bioactive and therapeutic compounds are diverse (Wei et al., 2013), and it is used in the treatment of hemoglobinopatheis, cancer, and gastrointestinal diseases (Huang et al., 2011b). In addition, butyric acid with direct hydrogenation in the presence of copper-based catalysts can produce promising fuel 1-butanol (Lim et al., 2013). It is synthesized commercially from petrochemical routes (Jiang et al., 2009a) by the oxidation of butyraldehyde through an oxoprocess using propylene and also by a novel synthesis method from maleic anhydride (Song et al., 2010). Due to the high demand and decreasing supply of world crude oil, the urgency of addressing the problem of increasing the production of butyric acid is becoming acute (Zhang et al., 2009).
1.3 COMMERCIALLY IMPORTANT PLATFORM CHEMICALS: ALCOHOLS
1.3.1
Xylitol
Xylitol, a five-carbon sugar alcohol, is an expensive polyol sweetener found in food products such as chewing gum, soft drinks, and confectionery (Sakakibara et al., 2009); it also has specific healthcare applications for oral health and parenteral nutrition (Rao et al., 2006). Xylitol is low-calorie pentitol. It is used as an anticariogenic and is an ideal sweetener for diabetics because its metabolism is not regulated by insulin and does not involve glucose 6-phosphate dehydrogenase (Cheng et al., 2009; Sakakibara et al., 2009). The industrial production of xylitol is through the chemical reduction of xylose derived from hydrolyzed plant materials, mainly birchwood chips, sugarcane bagasse (SCB), birch trees, and corn stalks
(Rao et al., 2006; Sakakibara et al., 2009). Annually around 30,000 tons of xylitol are produced by the chemical hydrogenation of xylose (Tamburini et al., 2010). The current xylitol market is around $340 million. The global consumption was 43,000 tons in 2005; the major consumers accounting, for 30% and 37%, respectively, were the United States and Western Europe. The chemical process of production is not ecofriendly, which further increases the capital investment and costs for xylitol production (Prakash et al., 2011).
1.3.2 Butanol
Butanol, an important C4 platform compound, is considered in particular replacements for liquid transportation fuels, and its properties make it superior to ethanol (Cooksley et al., 2012). Butanol has low volatility and is less corrosive and less hydroscopic (Cheng et al., 2012). It can be easily blended with petrol for its high energy content, low vapor pressure, and tolerance to water contamination. It gives better fuel economy than petrol–ethanol blends, with no need to make expensive modifications to car engines, and it can be blended into petrol at higher concentrations than ethanol (Cooksley et al., 2012). Butanol contains 22% oxygen and is an excellent fuel extender. It can be used, directly supplied, and stored through existing gasoline pipelines (Ni et al., 2013).
1.4 ADVANCES IN PLATFORM CHEMICAL PROCESS ENGINEERING: NATURAL MICROBIAL SYNTHESIS
1.4.1 3-Hydroxy-propionic Acid
The increasing commercial interests of 3-HP are toward exploring the biological methods of production using recombinant or fermentation processes over chemical synthesis. The major advantage of the microbial production of 3-HP is the ability to utilize significantly low-cost by-products of biodiesel production, which is rather simple and straightforward, involving two enzymes (Raj et al., 2009). 3-HP is found in several microorganisms, including bacteria, fungi, and yeast, as a key intermediate of their metabolism or as a secondary metabolite. It has been reported to play a role in the pathway for autotrophic carbon dioxide fixation, known as the 3-HP cycle. This cycle was first described in Chloroflexus aurantiacus, a facultative aerobic phototrophic bacterium (Holo, 1989). Other bacterial species are stated to synthesize 3-HP, eg, Rhodococcus erythropolis, Acidianus brierleyi, A. ambivalens, Sulfolobus metallic, and Metallosphaera sedula. 3-HP is also synthesized by recombinant Escherichiacoli strains. Suthers and Cameron (2005) claimed a patent for producing 3-HP using recombinant E.coli microorganism-carrying genetic constructs from Klebsiella pneumonia and a gene for aldehyde dehydrogenase, capable of producing 3-HP from glycerol (Suthers and Cameron, 2005). With the cloning of two genes, dhaB-encoding glycerol dehydratase and aldH-encoding aldehyde dehydrogenase, cultivated aerobically on glycerol, a medium-containing yeast extract produced 3-HP at a maximum concentration of 0.58 g/L (Raj et al., 2008). Studies involving a recombinant strain of K. pneumonia for the production of 3-HP using glycerol in a 5-l bioreactor under microaerobic conditions produced 16 g/L (Ashok et al., 2011) and under anaerobic fed-batch culture produced 24.4 g/L (Huang et al., 2012).
The production of 3-HP can be increased by using recombinant strains specific to carrying out a reductive pathway of glucose or glycerol degradation. Once glycerol is degraded via a reductive pathway, synthesis of 3-HP is carried out easily with the help of two enzymes: glycerol dehydratase and aldehyde dehydrogenase.
1.4.2 Lactic Acid
Microbial fermentation is a better alternative to chemical synthesis because optically pure lactic acid is produced, along with the utilization of renewable carbohydrates (Wang et al., 2010b). To meet the increasing demand, lactic acid is produced from various biomass such as garbage, potato starch, lignocellulosic biomass, and excess sludge by microbial fermentation (Maeda et al., 2009). Worldwide microbial fermentation accounts for around 90% of the total lactic acid production (Wang et al., 2010a). Lactic acid is commercially produced from starchy materials, but to reduce feedstock costs and avoid competition with the food supply, the use of low-cost, abundant, and renewable biomass as a carbon source has attracted attention (Ye et al., 2013).
Maeda et al. (2009) have investigated the development of a facile technology for effectively utilizing and/or reducing excess sewage sludge using endogenous bacteria from the sludge. When a 50 mM sucrose concentration in sludge was fermented at 50°C using seed inoculum, it resulted in 8.45 g/L high-lactic acid production and 38.2% sludge reduction with a conversion rate of up to 106.0%. The lactic acid bacteria were actually sludge-lysing bacteria and were able to produce lactic acid from protein and carbohydrates released from excess sludge (Maeda et al., 2009). Lignocellulosic biomass-derived sugars, such as low-cost corncob molasses, are considered to be an economically attractive carbohydrate feedstock for large-scale fermentations of lactic acid (Wang et al., 2010a). A waste by-product from xylitol production was used for lactic acid production; it was an encouraging process for the economical production of lactic acid.
The mixture of sugars, including xylose, arabinose, and glucose, in corncob molasses can be utilized by Bacillus sp. strain XZL9 at initial total sugars of 91.4 g/L for l-lactic acid (74.7 g/L) production in fed-batch fermentation. This study provides an economical lactic acid production process from low-cost lignocellulosic resources such as corncob molasses (Wang et al., 2010b). In another study by Wang et al. (2010b), a low-cost raw cassava-rich crop (in terms of carbohydrates) was powdered for the efficient production of lactic acid from Lactobacillus rhamnosus strain CASL. The efficiencies of various fermentation strategies, including simultaneous saccharification and fermentation (SSF), two-step fermentation (TSF), and simultaneous liquefaction, saccharification, and fermentation (SLSF), were investigated. A high l-lactic acid concentration (175.4 g/L) was obtained in a 5-L fermenter using 275 g/L of cassava powder concentration (carbon source 275 g/L) along with a yeast extract (5 g/L) in SSF batch fermentation at 1.8 g/L h productivity. This is the highest l-lactic acid concentration reported from a cassava source, suggesting SSF to be more economical and convenient in comparison to TSF and SLSF (Wang et al., 2010a). In a significant study by Taskin et al. (2012), the replacement of an expensive nitrogen source with a chicken feature containing 90% protein was used with molasses as a carbon source in the production of l-lactic acid. A chicken feather protein hydrolysate (CFP) containing 55.8 g/L of protein along with essential amino acids was sufficient for newly isolated Rhizopus oryzae TS-61 growth to produce 38.5 g/L concentrations of l-lactic. In contrast to yeast extract and ammonium sulfate, CFP provided a
smaller uniform pellet formation, prevented excessive pH changes, was a rich nitrogen supplement, reduced medium costs, and benefited the environmental problem by the utilization of waste (Taskin et al., 2012). Jawad et al. (2012) have investigated the production of lactic acid from mango peels under ambient conditions and optimized the production using a factorial design. A maximum production of 17.48 g/L highlights the potential of mango peels as a lowcost option, and process optimization will make the production of lactic acid economically viable and sustainable (Jawad et al., 2012).
The cost-effective production of optically pure lactic acid from lignocellulose sugars is commercially attractive but challenging. Ca(OH)2 was found to be a better neutralizing agent than NaOH in terms of its giving higher lactic acid titer and productivity. From a kinetic point of view, SSF, a two-reactor fermentation system, and a one-reactor repeated batch operation increased lactic acid production.
1.4.3 Fumaric Acid
Fumaric acid is among the top 12 chemicals produced by industrial fermentation. Due to a scarcity of petroleum worldwide, fermentation routes for fumaric acid production are gaining importance (Roa Engel et al., 2011). The fermentative production of these acids from renewable resources has received extensive attention worldwide and can replace fossil-based production via maleic acid (Deng et al., 2012).
Xu et al. (2010) have investigated a novel two-stage corn straw utilization strategy by the well-known producer R. oryzae for fumaric acid production. The pretreatment of corn straw after acid hydrolysis resulted in a xylose-rich liquid to be used for fungal growth and a residual glucose-rich liquid to be used for fumaric acid production. This two-stage corn straw utilization strategy resulted in 27.79 g/L fumaric acid production at a productivity of 0.33 g/L h (Xu et al., 2010).
In order to further increase fumaric acid production, R. oryzae ME-F12 was isolated and mutated to increase the activity of glucoamylase to develop SSF from starch materials without commercial glucoamylase supplementation. About 39.80 g/L of fumaric acid were successfully obtained using the mutant with 1.28-fold as compared to the parent strain, suggesting a new avenue for the cost-effective fermentation of fumaric acid (Deng et al., 2012).
Strain improvements for increased fumaric acid production with laser irradiation on R. oryzae were carried out to induce mutations. Following exposure to the irradiation, the mutant strain FM19 exhibited a 56.3% increased titer to produce 49.4 g/L of fumaric acid from glucose. The mutant strain followed carbon and amino acid metabolism and provided new insights into the metabolic characterization of a high-yielding fumaric acid strain (Yu et al., 2012).
A novel immobilization device using net and wire for filamentous R. arrhizus RH-07-13 for fumaric acid fermentation was developed. Abundant mycelia grew on a large surface of the net and consumed glucose rapidly with a transit of nutrients across the net, resulting in rapid fumaric acid production. The result was around 32.03 g/L of fumaric acid production, in comparison to free-cell fermentation (31.23 g/L), and a further reduction in fermentation time from 144 to 24 h (Gu et al., 2013).
Fumaric acid production can be increased by using the well-known producer Rhizopus strain, possessing high glucoamylase activity and maintaining conditions for mycelia growth for increased fumaric acid production at a reduced fermentation time.
1.4.4 Butyric Acid
Due to the use of butyric acid as an ingredient in food, cosmetics, and pharmaceutical applications, there is a high demand by consumers for bio-based butyric acid production (Jiang et al., 2009a). Butyric acid produced by fermentation is favored over chemically synthesized acids, and the food products get labeled as a “natural preservative” (Zhang et al., 2009). With the catalytic reaction of butyric acid and hydrogen, the most promising biofuels can be synthesized from microbial fermentation (Song et al., 2010). The dominant platform for the biological production of butyric acid is by using Clostridium sp., and some studies have focused on fermentation techniques, which are recombinant techniques to improve the productivity and titer of butyric acid.
To minimize the high share of carbon sources in the media component cost, the exploitation of cheap, renewable carbon sources has been stimulated. Cane molasses, a by-product of the sugar industry containing 45–50% total sugar, using attractive characteristics of immobilization for in batch, repeated-, and fed-batch fermentation in a fibrous-bed bioreactor (FBB) was carried out by Jiang et al. (2009a) The feasibility and robustness of the FBB system for producing butyric acid using low-cost cane molasses pretreated with sulfuric acid resulted in a 55.2 g/L increased production in comparison to batch fermentation (34.1 g/L) using C. tyrobutyricum (Jiang et al., 2009b). Similarly, Song et al. (2010) have proposed empirical kinetic models to determine the optimal operational condition and develop a proper substrate feeding strategy for fed-batch fermentation of C. tyrobutyricum. A model-based fed-batch fermentation with semicontinuous glucose feeding resulted in 73.77 g/L of butyric acid production, much higher than batch fermentation. The predictions of the models reported match with the fermentation data, showed improvement in production, and may contribute to developing a cost-effective butyric acid fermentation process (Song et al., 2010). Considering the cost efficiency of fermentation production, Jerusalem artichoke (JA), a relatively cheap and widely available nongrain raw material, was acid-hydrolyzed to generate fructose and glucose for butyric acid production. To compete with the petroleum route of production, an FBB with immobilized C. tyrobutyricum in a repeated-batch fermentation was successfully performed. The feasibility and efficiency of the FBB system with a high butyric acid concentration of 60.4 g/L from acid-pretreated JA hydrolysate could be achieved to compete with the petroleum route of production (Huang et al., 2011b). In a similar approach, an FBB with immobilized C. tyrobutyricum in a repeated-batch fermentation using SCB hydrolysate produced around 20.9 g/L of butyrate concentration (Wei et al., 2013).
These works demonstrate the feasibility of using low-cost feedstock, JA, and SCB for the efficient production of butyric acid. More studies on butyric acid production have focused on fed-batch fermentation, including an FBB using immobilized Clostridium. With advancements in genetic engineering, a redox cofactor regeneration system in E. coli was developed for the production of butyric acid. With the native redox cofactor regeneration system, butyrate was the only final electron acceptor. The demand of a cofactor was fulfilled for cellular growth and enabled the efficient conversion of glucose into butyric acid, reaching 83.4% of the theoretical maximum yield (Lim et al., 2013).
The best approach for increased butyric acid production is fed-batch fermentation, which showed the highest maximum cell density, minimized substrate loss, maximized the final titer, increased the yield of the target product, and showed pivotal importance for butyric acid production.
1.4.5 Xylitol
The chemical process is very expensive because of the high working temperature, application of pressure for the hydrogenation of xylose, and extensive steps for separation and purification. The industrial-scale production contains less xylose and other sugars such as arabinose, mannose, galatose, and glucose as major impurities (Sakakibara et al., 2009). From the economic viewpoint, the biotechnological production of xylitol seems to be very attractive, with the use of low-cost crude hemicellulosic hydrolysate as a potential substrate (Rao et al., 2006).
Corncob, the most abundant agricultural material, was chosen along with Candida tropicalis W103, capable of producing 200 g/L xylitol from xylose as the sole carbon source. The pretreatment step of acid hydrolysis on corncobs was followed by detoxification to reduce volatile and phenolic compounds. The effect of glucose in the hydrolysate promoted the growth of C. tropicalis, while the inhibition of acetate was alleviated by adjusting the pH to 6 prior to fermentation. Under these optimum conditions, 68.4 g/L of maximal xylitol concentration was obtained, giving a yield of 0.7 g/g xylose and a productivity of 0.95 g/L h (Cheng et al., 2009). Detoxification methods have been carried out to convert inhibitors to inactive compounds or reduce their concentration. Powdered activated charcoal was mixed with the hydrolysate at 2.5% (w/v) and stirred for 60 min; it enabled a reduction of furfural (58%) and total phenolic (78%) compounds, and the maximum xylitol concentration obtained was 19.53 g/L with a higher xylitol yield. The detoxification process of using low-cost activated charcoal strongly suggests an economical and significant impact in xylitol production (Kamal et al., 2011). After substrate hydrolysis, detoxification steps are necessary to minimize the inhibition of hydrolysate to improve microbial fermentation. A newly isolated yeast strain, C. tropicalis JH030, a high inhibitor tolerant to nondetoxified lignocellulosic hydrolysates, was developed for xylitol production. The applicability of isolated yeast to nondetoxified lignocellulosic hydrolysates derived from SCB and rice straw resulted in 26 and 46 g/L of xylitol production. The high inhibitor tolerant yeast’s using nondetoxified lignocellulosic hydrolysates enhanced the xylitol production and showed a practicable capacity on various other raw materials, such as silvergrass, napiergrass, and pineapple peel (Huang et al., 2011a).
A pretreatment process of steam explosion on SCB along with newly isolated thermotolerant strain Debaryomyces hansenii immobilized over Ca-alginate was carried out for xylitol production. The Ca-alginate immobilized system produced 73.8 g of xylitol in comparison to 68.6 g/L by free cells. The steam explosion pretreatment approach and immobilized system were reused for five batches with steady bioconversion rates and yields (Prakash et al., 2011).
Various microorganisms have been developed to produce xylitol from xylose, but some organisms do not have a xylose metabolic pathway. Genetic engineering has been adopted to express xylose reductase in recombinant Saccharomyces cerevisiae to be overexpressed for xylitol production. In-vitro activity analysis confirmed the functional expression of both enzymes: acetaldehyde dehydrogenase 6 (ALD6) and acetyl-CoA synthetase 1 (ACS1). The best result of xylitol production, 91.3 g/L xylitol concentration, was obtained by ACS1 overexpression, relative to those of the control and ALD6-overexpressing strains. The modulation of ALD6 and ACS1 in fed-batch fermentation showed the best xylitol concentration and productivity in comparison to other strains (Oh et al., 2013).
The main step in xylitol production is the pretreatment step to obtain an increased concentration of xylose in comparison to other undesired impurities. The pretreatment step adds
on impurities, for which the detoxification step is optional if a high inhibitor tolerant yeast strain capable of using nondetoxified lignocellulosic hydrolysates can be used, or genetically engineered strains capable of the best xylitol production can be developed.
1.4.6 Butanol
The increasing price of oil has led to a resurgence of interest in the microbial-based generation of biobutanol, in particular replacements for liquid fuels ( Cooksley et al., 2012 ). The important benefit of producing biobutanol is that it can be produced from various low-cost substrates and does not require supplementation of external enzymes, as butanol-producing strains produce hydrolysis enzymes ( Qureshi et al., 2013 ). Biobutanol production largely depends on the availability of low-cost, abundant raw materials and an efficient process conversion into butanol production. Soon after substrate hydrolysis, detoxification treatment fails to remove inhibitors completely. A membrane-filtered sugar maple wood extract hydrolysate was used to produce butanol. Using nanofiltration, the membrane could remove all small molecular organic acids such as acetic acid and formic acid. The treatment significantly improved the butanol concentration to 7 from 0.8 g/L ( Sun and Liu, 2012 ).
Microorganisms having a high tolerance toward solvents are beneficial for butanol production and to avoid product inhibition. Highly efficient butanol-producing bacteria belonging to Clostridium sp. were isolated from sludge of a sewage treatment plant. The maximum butanol concentration of 12.4 g/L with the addition of 6.0 g/L butyric acid, the pathway for butanol production, was triggered with the titer significantly increased to 17.51 ± 0.49 g/L. Using a 5-L fermenter with a pressurized fermentation strategy enhanced the butanol concentration to 21.1 g/L, and this was accomplished by inhibiting hydrogen production (Cheng et al., 2012).
C. beijerinckii ATCC 10,132 during butanol production demonstrated the ability to accumulate rhodamine 6 G, accompanied by an increased expression of the chaperone, and showed a high tolerance to 25 g/L n-butanol under optimized conditions. The strain reported for a high titer of butanol of 20 g/L without resorting to solvent stripping or strain improvement (Isar and Rangaswamy, 2012).
The recovery of butanol from fermentation broth is necessary to avoid product inhibition. The use of the hyperbutanol-producing C. acetobutylicum strain in an FBB under continuous butanol recovery was studied using concentrated cassava bagasse hydrolysate. The stable production of n-butanol with a periodic nutrient supply resulted in 76.4 g/L of butanol production. With gas stripping, long-term stability, improved fermentation kinetics, and continuous butanol production, the process is attractive for industrial production (Lu et al., 2012).
Butanol-enriched biodiesel can improve the fuel properties of blends, with biodiesel as an extractant-enhanced butanol production. The in situ butanol removal by the addition of biodiesel resulted in a maximum total butanol of around 31.44 g/L and had no significant toxicity on the growth of C. acetobutylicum, showing great potential for commercial butanol production (Yen and Wang, 2013).
To increase butanol production, it is very important to use high solvent tolerant butanolproducing bacteria, a requirement of simple sugar with no addition of external hydrolyzing enzymes. The most important parameter is to continuously recover the produced butanol from fermentation.
1.5 CHALLENGES AND FUTURE OF THE INDUSTRY
1.5.1 3-Hydroxy-propionic
In the case of 3-HP, production through the biological method had many hurdles, and the final titer was too low to be considered for commercial applications. The physicochemical parameters, such as pH, liquid-to-flasks volume ratio, and substrate concentration, under batch and fed-batch conditions were investigated. With parameter optimization under the fed-batch process using the recombinant under glycerol as the sole carbon source, 3-HP at 31 g/L with a yield of 35% was produced, near to a commercially meaningful level (Raj et al., 2009).
1.5.2 Lactic Acid
The production of optically pure lactic acid from sugar is commercially attractive but challenging. Due to large amounts of acetic acid coproduction, the cost of lactic acid separation and purification significantly increases. Ye et al. (2013) used Bacillus coagulans C106 to produce optically pure lactic acid and followed the pentose pathway with a minimum amount of acetic acid production. During batch and fed-batch fermentation with xylose as the substrate, the lactic acid titer reached 83.6 g/L and 215.7 g/L, respectively, with optical purity of 99.6% in both cases. The lactic acid titer and productivity are the highest among those ever reported from xylose (Ye et al., 2013).
1.5.3 Fumaric Acid
Fumaric acid production by fermentation can be improved by minimizing the use of neutralizing agents, maintaining the morphology of fungi, or by using metabolic engineering to achieve higher fumaric acid production. However, most of the fermentation processes are carried out at a final pH in the range of 4.5–6.5, requiring the addition of bases such as NaOH and CaCO3 to control the pH (Roa Engel et al., 2008). Roa Engel et al. (2011) have developed several new approaches to minimize inorganic acid and base consumption and waste salt production. The authors have shown that fumaric acid fermentation can be done at a relatively low pH (3.6) with R. oryzae. These fermentations consume CO2 to obtain a clean process and also minimize product inhibition in the absence of neutralizing agents. Fumaric acid, which has a low aqueous solubility, was directly recovered from the fermentation broth by cooling crystallization. This leads to a very simple production procedure, which might be improved if an even lower fermentation pH was achieved (Roa Engel et al., 2011).
1.5.4 Butyric Acid
Improvement in the productivity of butyric acid by including engineering-based strains, the utilization of low-cost feedstocks, and the application of an FBB along with fed-batch fermentation needs effective strategies to separate butyric acid from fermentation broth. The solvent toxicity increases during extraction, and a huge energy consumption during distillation prohibits their application in the separation of butyric acid. A novel aqueous two-phase partition system using calcium chloride for the effective phase separation of butyric acid from fermentation broth was developed. This “salting out” effect increased the butyric acid/acetic acid concentration in the upper phase to 9.87, which was initially around 4:1. The aqueous
two-phase system provides an effective and promising way to separate butyric acid from fermentation broth (Wu et al., 2010).
1.5.5 Xylitol
Xylitol produced during fermentation is always separated and purified by chromatographic methods, which tend to be expensive for industrial-scale processes. With liquid–liquid extraction and precipitation techniques, the solvents used make xylitol recovery difficult and expensive for large-scale purification. A strategy for xylitol extraction using an activated charcoal treatment step followed by a vacuum concentration and crystallization method was carried out. The activated charcoal treatment followed by 15.0 g/L of charcoal concentration at 30°C for 1 h with 10 times super saturation of the initial concentration resulted in clear, large crystals of xylitol. The crystallization temperature of −20°C for initiation and 8°C after four cycles of crystallization resulted in a 76.20% xylitol crystallization yield. The purity of the xylitol was 98.99%, suggesting a cost-effective, efficient, easy, less time-consuming, and environmental friendly procedure (Misra et al., 2011).
1.5.6 Butanol
The only way to increase the economic efficacy of butanol fermentation is to increase its concentration by eliminating the production of undesired by-products. C. acetobutylicum EA 2018 was disrupted with an acetoacetate decarboxylase gene (adc) into a hyper butanol-producing industrial strain using TargeTron technology. The undesired by-product acetone production reduced with butanol concentration increased from 70% to 80.05%. A simple approach of blocking acetone production by Clostridium demonstrates the industrial potential of this strain for butanol production (Jiang et al., 2009b). The performance of fermentative butanol production quantitatively depends on the tolerance of solvent-producing bacteria. With a Clostridial species-dominated bacterial consortium the maximal butanol production was 10.64 ± 0.60 g/L and with tolerant butanol the concentration level was 16 g/L (Chen et al., 2012). With artificial simulation of bioevolution (ASBE) based on the evolutionary dynamics and natural selection a high butanol tolerance to C. acetobutylicum was developed. The increase of butanol production from 12.2 g/L to 15.3 g/L using corn meal as a substrate suggested that the ASBE method of enhancing butanol tolerance increased butanol production (Liu et al., 2013).
1.6 CONCLUSION
Platform chemicals have an undeniable commercial importance, and at present they are mainly produced from petroleum-based raw materials. Owing to the finite nature of fossilderived feedstock as well as environmental concerns, the sustainable manufacturing of platform chemicals using biomass-based substrates is becoming inevitable. In this context, advances in renewable platform chemical manufacturing have been summarized in the present literature survey. The screening of less expensive feedstock, a process designed for maximum substrate utilization, the development of more efficient microbial strains, integrated downstream processing techniques, and green manufacturing are the major areas of platform chemical biorefinery where further research should be focused.
Acknowledgments
The authors are thankful to CRIQ, Quebec, for financial as well as technical assistance.
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