Recent advances on production of 2, 3-butanediol using engineered microbes.

As a significant platform chemical, 2, 3-butanediol (2, 3-BD) has found wide applications in industry. The success of microbial 2, 3-BD production was limited by the use of pathogenic microorganisms and low titer in engineered hosts. The utilization of cheaply available feedstock such as lignocellulose was another major challenge to achieve economic production of 2, 3-BD. To address those issues, engineering strategies including both genetic modifications and process optimization have been employed. In this review, we summarized the state-of-the-art progress in the biotechnological production of 2, 3-BD. Metabolic engineering and process engineering strategies were discussed.

[1]  Ana Rute Neves,et al.  Stereospecificity of Corynebacterium glutamicum 2,3-butanediol dehydrogenase and implications for the stereochemical purity of bioproduced 2,3-butanediol , 2016, Applied Microbiology and Biotechnology.

[2]  Xiao-Jun Ji,et al.  Constructing a synthetic metabolic pathway in Escherichia coli to produce the enantiomerically pure (R, R)-2,3-butanediol. , 2015, Biotechnology and bioengineering.

[3]  S. Atsumi,et al.  Cyanobacterial conversion of carbon dioxide to 2,3-butanediol , 2013, Proceedings of the National Academy of Sciences.

[4]  H. Woo,et al.  Enhanced 2,3-Butanediol Production by Optimizing Fermentation Conditions and Engineering Klebsiella oxytoca M1 through Overexpression of Acetoin Reductase , 2015, PloS one.

[5]  Hongwu Ma,et al.  Metabolic engineering of Bacillus subtilis for chiral pure meso-2,3-butanediol production , 2016, Biotechnology for Biofuels.

[6]  Yong‐Su Jin,et al.  Production of 2,3-butanediol by engineered Saccharomyces cerevisiae. , 2013, Bioresource technology.

[7]  Z. Xiu,et al.  Enhanced Production of 2,3-Butanediol from Sugarcane Molasses , 2015, Applied Biochemistry and Biotechnology.

[8]  Hyohak Song,et al.  Metabolic engineering of Klebsiella pneumoniae based on in silico analysis and its pilot-scale application for 1,3-propanediol and 2,3-butanediol co-production , 2017, Journal of Industrial Microbiology & Biotechnology.

[9]  Min-Kyu Oh,et al.  Metabolic engineering of Enterobacter aerogenes for 2,3-butanediol production from sugarcane bagasse hydrolysate. , 2017, Bioresource technology.

[10]  J. Hahn,et al.  Efficient production of 2,3-butanediol in Saccharomyces cerevisiae by eliminating ethanol and glycerol production and redox rebalancing. , 2015, Metabolic engineering.

[11]  T. Ohtsuki,et al.  Characterization of the NADH-linked acetylacetoin reductase/2,3-butanediol dehydrogenase gene from Bacillus cereus YUF-4. , 2001, Journal of bioscience and bioengineering.

[12]  Shangtian Yang,et al.  Improved Production of 2,3-Butanediol in Bacillus amyloliquefaciens by Over-Expression of Glyceraldehyde-3-Phosphate Dehydrogenase and 2,3-butanediol Dehydrogenase , 2013, PloS one.

[13]  Yu Wang,et al.  Glycerol Dehydrogenase Plays a Dual Role in Glycerol Metabolism and 2,3-Butanediol Formation in Klebsiella pneumoniae * , 2014, The Journal of Biological Chemistry.

[14]  K. Kim,et al.  Enhanced production of 2,3-butanediol by engineered Saccharomyces cerevisiae through fine-tuning of pyruvate decarboxylase and NADH oxidase activities , 2016, Biotechnology for Biofuels.

[15]  Jin-Ho Seo,et al.  Enhanced production of 2,3-butanediol from xylose by combinatorial engineering of xylose metabolic pathway and cofactor regeneration in pyruvate decarboxylase-deficient Saccharomyces cerevisiae. , 2017, Bioresource technology.

[16]  S. Atsumi,et al.  Combinatorial optimization of cyanobacterial 2,3-butanediol production. , 2014, Metabolic engineering.

[17]  Zhen Fang,et al.  Production of 2,3-butanediol from acid hydrolysates of Jatropha hulls with Klebsiella oxytoca. , 2012, Bioresource technology.

[18]  T. Ohtsuki,et al.  Purification and Characterization of L-2,3-Butanediol Dehydrogenase of Brevibacterium saccharolyticum C-1012 Expressed in Escherichia coli , 2001, Bioscience, biotechnology, and biochemistry.

[19]  J. Carballo,et al.  Purification, characterization and some properties of diacetyl(acetoin) reductase from Enterobacter aerogenes. , 1991, European journal of biochemistry.

[20]  Y. Ni,et al.  Cloning, Expression, and Characterization of budC Gene Encoding meso-2,3-Butanediol Dehydrogenase from Bacillus licheniformis , 2016, Applied Biochemistry and Biotechnology.

[21]  Ping Xu,et al.  Efficient production of 2,3-butanediol from corn stover hydrolysate by using a thermophilic Bacillus licheniformis strain. , 2014, Bioresource technology.

[22]  Daun Jeong,et al.  Redistribution of Carbon Flux toward 2,3-Butanediol Production in Klebsiella pneumoniae by Metabolic Engineering , 2014, PloS one.

[23]  Syed Shams Yazdani,et al.  Efficient production of (R,R)-2,3-butanediol from cellulosic hydrolysate using Paenibacilluspolymyxa ICGEB2008 , 2014, Journal of Industrial Microbiology & Biotechnology.

[24]  D. Wei,et al.  Mechanism of 2,3-butanediol stereoisomer formation in Klebsiella pneumoniae , 2014, Applied Microbiology and Biotechnology.

[25]  Marzena Jędrzejczak-Krzepkowska,et al.  Application of enzymatic apple pomace hydrolysate to production of 2,3-butanediol by alkaliphilic Bacillus licheniformis NCIMB 8059 , 2015, Journal of Industrial Microbiology & Biotechnology.

[26]  A. Białkowska Strategies for efficient and economical 2,3-butanediol production: new trends in this field , 2016, World journal of microbiology & biotechnology.

[27]  A. Lali,et al.  A shortened, two-enzyme pathway for 2,3-butanediol production in Escherichia coli , 2017, Journal of Industrial Microbiology & Biotechnology.

[28]  Jibin Sun,et al.  Novel (2R,3R)-2,3-Butanediol Dehydrogenase from Potential Industrial Strain Paenibacillus polymyxa ATCC 12321 , 2011, Applied and Environmental Microbiology.

[29]  Tamotsu Hoshino,et al.  Establishment of a novel gene expression method, BICES (biomass-inducible chromosome-based expression system), and its application to the production of 2,3-butanediol and acetoin. , 2014, Metabolic engineering.

[30]  Huadong Pei,et al.  Effect of the inactivation of lactate dehydrogenase, ethanol dehydrogenase, and phosphotransacetylase on 2,3-butanediol production in Klebsiella pneumoniae strain , 2014, Biotechnology for Biofuels.

[31]  Chun Li,et al.  Cloning, expression and characterization of meso-2,3-butanediol dehydrogenase from Klebsiella pneumoniae , 2012, Biotechnology Letters.

[32]  M. Oh,et al.  Alleviation of carbon catabolite repression in Enterobacter aerogenes for efficient utilization of sugarcane molasses for 2,3-butanediol production , 2015, Biotechnology for Biofuels.

[33]  Dehua Liu,et al.  Enzymatic hydrolysis and simultaneous saccharification and fermentation of alkali/peracetic acid-pretreated sugarcane bagasse for ethanol and 2,3-butanediol production. , 2011, Enzyme and microbial technology.

[34]  Won-Kyung Hong,et al.  Enhancement of 2,3-butanediol production from Jerusalem artichoke tuber extract by a recombinant Bacillus sp. strain BRC1 with increased inulinase activity , 2017, Journal of Industrial Microbiology & Biotechnology.

[35]  Shang-Tian Yang,et al.  Fermentation of biodiesel-derived glycerol by Bacillus amyloliquefaciens: effects of co-substrates on 2,3-butanediol production , 2013, Applied Microbiology and Biotechnology.

[36]  Ping Xu,et al.  Metabolic engineering of Escherichia coli for production of (2S,3S)-butane-2,3-diol from glucose , 2015, Biotechnology for Biofuels.

[37]  Shang-Tian Yang,et al.  Economic conversion of spirit-based distillers’ grain to 2,3-butanediol by Bacillus amyloliquefaciens , 2015 .

[38]  Jong Myoung Park,et al.  In silico aided metabolic engineering of Klebsiella oxytoca and fermentation optimization for enhanced 2,3-butanediol production , 2013, Journal of Industrial Microbiology & Biotechnology.

[39]  Sylvie Dequin,et al.  Enantioselective Synthesis of Vicinal (R,R)-Diols by Saccharomyces cerevisiae Butanediol Dehydrogenase , 2016, Applied and Environmental Microbiology.

[40]  Michael Köpke,et al.  2,3-Butanediol Production by Acetogenic Bacteria, an Alternative Route to Chemical Synthesis, Using Industrial Waste Gas , 2011, Applied and Environmental Microbiology.

[41]  Cuiqing Ma,et al.  Systematic metabolic engineering of Escherichia coli for high-yield production of fuel bio-chemical 2,3-butanediol. , 2014, Metabolic engineering.

[42]  Hong Xu,et al.  A 2,3‐butanediol dehydrogenase from Paenibacillus polymyxa ZJ‐9 for mainly producing R,R‐2,3‐butanediol: Purification, characterization and cloning , 2013, Journal of basic microbiology.

[43]  Parameswaran Binod,et al.  Evaluation of oil palm front hydrolysate as a novel substrate for 2,3-butanediol production using a novel isolate Enterobacter cloacae SG1 , 2016 .

[44]  Klaas J Hellingwerf,et al.  Synthesis of 2,3-butanediol by Synechocystis sp. PCC6803 via heterologous expression of a catabolic pathway from lactic acid- and enterobacteria. , 2013, Metabolic engineering.

[45]  Li Sha,et al.  BIOTECHNOLOGICALLY RELEVANT ENZYMES AND PROTEINS A new NAD(H)-dependent meso-2,3-butanediol dehydrogenase from an industrially potential strain Serratia marcescens H30 , 2014 .

[46]  Yong-Su Jin,et al.  Production of 2,3-butanediol from xylose by engineered Saccharomyces cerevisiae. , 2014, Journal of biotechnology.

[47]  Ana Rute Neves,et al.  Engineering Corynebacterium glutamicum for the production of 2,3-butanediol , 2015, Microbial Cell Factories.

[48]  Jinwon Lee,et al.  Industrial Production of 2,3-Butanediol from the Engineered Corynebacterium glutamicum , 2015, Applied Biochemistry and Biotechnology.

[49]  M. Oh,et al.  Deletion of lactate dehydrogenase in Enterobacter aerogenes to enhance 2,3-butanediol production , 2012, Applied Microbiology and Biotechnology.

[50]  R. Jain,et al.  Engineering of Bacillus subtilis for the Production of 2,3-Butanediol from Sugarcane Molasses , 2016, Applied Biochemistry and Biotechnology.

[51]  Zhao Wang,et al.  Characterization of a stereospecific acetoin(diacetyl) reductase from Rhodococcus erythropolis WZ010 and its application for the synthesis of (2S,3S)-2,3-butanediol , 2013, Applied Microbiology and Biotechnology.

[52]  Shujing Sun,et al.  Cloning, expression and characterization of glycerol dehydrogenase involved in 2,3-butanediol formation in Serratia marcescens H30 , 2014, Journal of Industrial Microbiology & Biotechnology.

[53]  K. Jantama,et al.  Efficient reduction of the formation of by-products and improvement of production yield of 2,3-butanediol by a combined deletion of alcohol dehydrogenase, acetate kinase-phosphotransacetylase, and lactate dehydrogenase genes in metabolically engineered Klebsiella oxytoca in mineral salts medium. , 2015, Metabolic engineering.

[54]  Cuiqing Ma,et al.  Contracted but effective: production of enantiopure 2,3-butanediol by thermophilic and GRAS Bacillus licheniformis , 2016 .

[55]  Min Zhang,et al.  Zymomonas mobilis as a model system for production of biofuels and biochemicals , 2016, Microbial biotechnology.

[56]  Jinwon Lee,et al.  Synthesis of Pure meso-2,3-Butanediol from Crude Glycerol Using an Engineered Metabolic Pathway in Escherichia coli , 2012, Applied Biochemistry and Biotechnology.

[57]  Zhiyou Wen,et al.  Deletion of meso-2,3-butanediol dehydrogenase gene budC for enhanced D-2,3-butanediol production in Bacillus licheniformis , 2014, Biotechnology for Biofuels.

[58]  Huimin Zhao,et al.  Metabolic engineering of a Saccharomyces cerevisiae strain capable of simultaneously utilizing glucose and galactose to produce enantiopure (2R,3R)-butanediol. , 2014, Metabolic engineering.

[59]  M. Oh,et al.  Production of 2,3-butanediol in Saccharomyces cerevisiae by in silico aided metabolic engineering , 2011, Microbial Cell Factories.

[60]  Jang-Min Park,et al.  Identification and characterization of a short-chain acyl dehydrogenase from Klebsiella pneumoniae and its application for high-level production of l-2,3-butanediol , 2014, Journal of Industrial Microbiology & Biotechnology.

[61]  X. Parés,et al.  Characterization of a (2R,3R)-2,3-Butanediol Dehydrogenase as theSaccharomyces cerevisiae YAL060W Gene Product , 2000, The Journal of Biological Chemistry.

[62]  M. Oh,et al.  Enhanced 2,3-butanediol production in recombinant Klebsiella pneumoniae via overexpression of synthesis-related genes. , 2012, Journal of microbiology and biotechnology.

[63]  D. Xiao,et al.  Enhanced production of 2,3‐butanediol by overexpressing acetolactate synthase and acetoin reductase in Klebsiella pneumoniae , 2014, Biotechnology and applied biochemistry.

[64]  Cuiqing Ma,et al.  Metabolic engineering of Enterobacter cloacae for high-yield production of enantiopure (2R,3R)-2,3-butanediol from lignocellulose-derived sugars. , 2015, Metabolic engineering.

[65]  Zhiyou Wen,et al.  Engineering Bacillus licheniformis for the production of meso-2,3-butanediol , 2016, Biotechnology for Biofuels.

[66]  Peter Ruhdal Jensen,et al.  Combining metabolic engineering and biocompatible chemistry for high-yield production of homo-diacetyl and homo-(S,S)-2,3-butanediol. , 2016, Metabolic engineering.

[67]  Jin-Ho Seo,et al.  Molecular cloning and expression of Enterobacter aerogenes α-acetolactate decarboxylase in pyruvate decarboxylase-deficient Saccharomyces cerevisiae for efficient 2,3-butanediol production , 2016 .

[68]  Paola Pedrini,et al.  New acetoin reductases from Bacillus stearothermophilus: meso- and 2R,3R-butanediol as fermentation products , 2011 .

[69]  Dae-Hyuk Kim,et al.  Enhanced production of 2,3-butanediol by a genetically engineered Bacillus sp. BRC1 using a hydrolysate of empty palm fruit bunches , 2015, Bioprocess and Biosystems Engineering.

[70]  X. Guan,et al.  Mechanism of 2,3-butanediol stereoisomers formation in a newly isolated Serratia sp. T241 , 2016, Scientific Reports.

[71]  Tomohisa Hasunuma,et al.  Cocktail δ-integration of xylose assimilation genes for efficient ethanol production from xylose in Saccharomyces cerevisiae. , 2013, Journal of bioscience and bioengineering.

[72]  W. Grajek,et al.  Biotechnological production of 2,3-butanediol--current state and prospects. , 2009, Biotechnology advances.

[73]  Miguel Ladero,et al.  Novel biocatalysts for glycerol conversion into 2,3-butanediol , 2016 .

[74]  Stephen S Fong,et al.  Study of ChiR function in Serratia marcescens and its application for improving 2,3-butanediol from crystal chitin , 2017, Applied Microbiology and Biotechnology.

[75]  Jianzhong Shao,et al.  Characterization of a (2R,3R)-2,3-Butanediol Dehydrogenase from Rhodococcus erythropolis WZ010 , 2015, Molecules.

[76]  Jun Yuan,et al.  Utilization of Sweet Sorghum Juice for Efficient 2,3-Butanediol Production by Serratia marcescens H30 , 2017 .

[77]  Daun Jeong,et al.  A non-pathogenic and optically high concentrated (R,R)-2,3-butanediol biosynthesizing Klebsiella strain. , 2015, Journal of biotechnology.

[78]  M. Penttilä,et al.  Characterization of the genes of the 2,3-butanediol operons from Klebsiella terrigena and Enterobacter aerogenes , 1993, Journal of bacteriology.

[79]  H. Woo,et al.  High production of 2,3-butanediol from biodiesel-derived crude glycerol by metabolically engineered Klebsiella oxytoca M1 , 2015, Biotechnology for Biofuels.

[80]  Dongzhi Wei,et al.  Characterization and regulation of the 2,3-butanediol pathway in Serratia marcescens , 2011, Applied Microbiology and Biotechnology.

[81]  Wayne M Patrick,et al.  Reconstruction of an Acetogenic 2,3-Butanediol Pathway Involving a Novel NADPH-Dependent Primary-Secondary Alcohol Dehydrogenase , 2014, Applied and Environmental Microbiology.

[82]  Denise Molinnus,et al.  (R,R)-Butane-2,3-diol dehydrogenase from Bacillus clausii DSM 8716T: Cloning and expression of the bdhA-gene, and initial characterization of enzyme. , 2017, Journal of biotechnology.

[83]  Zisheng Zhang,et al.  Production of (2R, 3R)-2,3-butanediol using engineered Pichia pastoris: strain construction, characterization and fermentation , 2018, Biotechnology for Biofuels.

[84]  P. Ouyang,et al.  Microbial 2,3-butanediol production: a state-of-the-art review. , 2011, Biotechnology advances.

[85]  Yong-Su Jin,et al.  Expression of Lactococcus lactis NADH oxidase increases 2,3-butanediol production in Pdc-deficient Saccharomyces cerevisiae. , 2015, Bioresource technology.

[86]  Zhenghong Xu,et al.  The rebalanced pathway significantly enhances acetoin production by disruption of acetoin reductase gene and moderate-expression of a new water-forming NADH oxidase in Bacillus subtilis. , 2014, Metabolic engineering.

[87]  Zi-Yong Liu,et al.  Characterization of an acetoin reductase/2,3-butanediol dehydrogenase from Clostridium ljungdahlii DSM 13528. , 2015, Enzyme and microbial technology.

[88]  Minoru Takeda,et al.  Identification and Characterization of a Mycobacterial (2R,3R)-2,3-Butanediol Dehydrogenase , 2011, Bioscience, biotechnology, and biochemistry.

[89]  Ryosuke Yamada,et al.  Efficient production of 2,3-butanediol by recombinant Saccharomyces cerevisiae through modulation of gene expression by cocktail δ-integration. , 2017, Bioresource technology.

[90]  Z. Rao,et al.  Identification and characterization of a novel 2,3‐butanediol dehydrogenase/acetoin reductase from Corynebacterium crenatum SYPA5‐5 , 2015, Letters in applied microbiology.

[91]  J. van der Oost,et al.  d-2,3-Butanediol Production Due to Heterologous Expression of an Acetoin Reductase in Clostridium acetobutylicum , 2011, Applied and Environmental Microbiology.

[92]  Akihiko Kondo,et al.  2,3-Butanediol production from cellobiose using exogenous beta-glucosidase-expressing Bacillus subtilis , 2016, Applied Microbiology and Biotechnology.

[93]  Cuiqing Ma,et al.  Enhanced 2,3-butanediol production by Klebsiella pneumoniae SDM , 2009, Applied Microbiology and Biotechnology.

[94]  W. Nicholson The Bacillus subtilis ydjL (bdhA) Gene Encodes Acetoin Reductase/2,3-Butanediol Dehydrogenase , 2008, Applied and Environmental Microbiology.

[95]  Servé W. M. Kengen,et al.  Molecular Characterization of an NADPH-Dependent Acetoin Reductase/2,3-Butanediol Dehydrogenase from Clostridium beijerinckii NCIMB 8052 , 2014, Applied and Environmental Microbiology.

[96]  Shangtian Yang,et al.  Enhanced 2,3-butanediol production from biodiesel-derived glycerol by engineering of cofactor regeneration and manipulating carbon flux in Bacillus amyloliquefaciens , 2015, Microbial Cell Factories.

[97]  M. Himmel,et al.  Metabolic engineering of Zymomonas mobilis for 2,3-butanediol production from lignocellulosic biomass sugars , 2016, Biotechnology for Biofuels.

[98]  Seraphim Papanikolaou,et al.  Production of 1,3-propanediol, 2,3-butanediol and ethanol by a newly isolated Klebsiella oxytoca strain growing on biodiesel-derived glycerol based media , 2012 .

[99]  Tao Chen,et al.  NADH plays the vital role for chiral pure D-(-)-2,3-butanediol production in Bacillus subtilis under limited oxygen conditions. , 2014, Biotechnology and bioengineering.

[100]  Klaas J Hellingwerf,et al.  Engineering cyanobacteria for direct biofuel production from CO2. , 2015, Current opinion in biotechnology.

[101]  Ping Xu,et al.  Efficient Simultaneous Saccharification and Fermentation of Inulin to 2,3-Butanediol by Thermophilic Bacillus licheniformis ATCC 14580 , 2014, Applied and Environmental Microbiology.

[102]  Xiao-Jun Ji,et al.  Constructing a synthetic constitutive metabolic pathway in Escherichia coli for (R, R)-2,3-butanediol production , 2015, Applied Microbiology and Biotechnology.

[103]  Shang-Tian Yang,et al.  Metabolic engineering of Bacillus subtilis for redistributing the carbon flux to 2,3-butanediol by manipulating NADH levels , 2015, Biotechnology for Biofuels.

[104]  Youngsoon Um,et al.  High production of 2,3-butanediol from glycerol without 1,3-propanediol formation by Raoultella ornithinolytica B6 , 2017, Applied Microbiology and Biotechnology.

[105]  Min-Kyu Oh,et al.  Reutilization of green liquor chemicals for pretreatment of whole rice waste biomass and its application to 2,3-butanediol production. , 2016, Bioresource technology.

[106]  Yong-Su Jin,et al.  2,3-Butanediol production from cellobiose by engineered Saccharomyces cerevisiae , 2014, Applied Microbiology and Biotechnology.

[107]  Shangtian Yang,et al.  Regulation of the NADH pool and NADH/NADPH ratio redistributes acetoin and 2,3-butanediol proportion in Bacillus subtilis. , 2015, Biotechnology journal.

[108]  Shuiquan Tang,et al.  Pichia pastoris fermentation for phytase production using crude glycerol from biodiesel production as the sole carbon source. , 2009 .