Production of 3-Hydroxypropionic Acid from Renewable Substrates by Metabolically Engineered Microorganisms: A Review

3-Hydroxypropionic acid (3-HP) is a platform chemical with a wide range of existing and potential applications, including the production of poly(3-hydroxypropionate) (P-3HP), a biodegradable plastic. The microbial synthesis of 3-HP has attracted significant attention in recent years due to its green and sustainable properties. In this paper, we provide an overview of the microbial synthesis of 3-HP from four major aspects, including the main 3-HP biosynthesis pathways and chassis strains used for the construction of microbial cell factories, the major carbon sources used for 3-HP production, and fermentation processes. Recent advances in the biosynthesis of 3-HP and related metabolic engineering strategies are also summarized. Finally, this article provides insights into the future direction of 3-HP biosynthesis.

[1]  Arthur J. Ragauskas,et al.  Biocatalytic gateway to convert glycerol into 3-hydroxypropionic acid in waste-based biorefineries: Fundamentals, limitations, and potential research strategies. , 2022, Biotechnology advances.

[2]  S. Lee,et al.  Systems metabolic engineering of Corynebacterium glutamicum for the efficient production of β-alanine. , 2022, Metabolic engineering.

[3]  Q. Fei,et al.  Efficient biosynthesis of 3-hydroxypropionic acid from ethanol in metabolically engineered Escherichia coli. , 2022, Bioresource technology.

[4]  P. Ferrer,et al.  Combining Metabolic Engineering and Multiplexed Screening Methods for 3-Hydroxypropionic Acid Production in Pichia pastoris , 2022, Frontiers in Bioengineering and Biotechnology.

[5]  Q. Nie,et al.  Recent advances, challenges and metabolic engineering strategies in the biosynthesis of 3‐hydroxypropionic acid , 2022, Biotechnology and bioengineering.

[6]  Peng Zhao,et al.  Engineering Glucose-to-Glycerol Pathway in Klebsiella pneumoniae and Boosting 3-Hydroxypropionic Acid Production Through CRISPR Interference , 2022, Frontiers in Bioengineering and Biotechnology.

[7]  J. Rodrigues Heterologous Production of Acrylic Acid: Current Challenges and Perspectives , 2022, SynBio.

[8]  Qian Wang,et al.  The Expression Modulation of the Key Enzyme Acc for Highly Efficient 3-Hydroxypropionic Acid Production , 2022, Frontiers in Microbiology.

[9]  Hongwu Ma,et al.  Enhanced 3-Hydroxypropionic Acid Production From Acetate via the Malonyl-CoA Pathway in Corynebacterium glutamicum , 2022, Frontiers in Bioengineering and Biotechnology.

[10]  V. Gupta,et al.  Valorisation of xylose to renewable fuels and chemicals, an essential step in augmenting the commercial viability of lignocellulosic biorefineries , 2021, Sustainable energy & fuels.

[11]  Peng Hu,et al.  One stone two birds: Biosynthesis of 3-hydroxypropionic acid from CO2 and syngas-derived acetic acid in Escherichia coli , 2021, Synthetic and systems biotechnology.

[12]  Peng Zhao,et al.  Biosynthesis pathways and strategies for improving 3-hydroxypropionic acid production in bacteria , 2021, World Journal of Microbiology and Biotechnology.

[13]  D. Freire,et al.  Benchmarking recombinant Pichia pastoris for 3‐hydroxypropionic acid production from glycerol , 2021, Microbial biotechnology.

[14]  H. Zabed,et al.  Notable Improvement of 3-Hydroxypropionic Acid and 1,3-Propanediol Coproduction Using Modular Coculture Engineering and Pathway Rebalancing , 2021 .

[15]  Guoqiang Chen,et al.  Hyperproduction of 3-hydroxypropionate by Halomonas bluephagenesis , 2021, Nature Communications.

[16]  Peng Zhao,et al.  Switching metabolic flux by engineering tryptophan operon-assisted CRISPR interference system in Klebsiella pneumoniae. , 2021, Metabolic engineering.

[17]  Sunghoon Park,et al.  Development of Pseudomonas asiatica as a host for the production of 3-hydroxypropionic acid from glycerol. , 2021, Bioresource technology.

[18]  Sunghoon Park,et al.  Production of 3-hydroxypropionic acid from acetate using metabolically-engineered and glucose-grown Escherichia coli. , 2020, Bioresource technology.

[19]  Marius Henkel,et al.  From Acetate to Bio-Based Products: Underexploited Potential for Industrial Biotechnology. , 2020, Trends in biotechnology.

[20]  Peng Zhao,et al.  Intensifying niacin-based biosynthesis of NAD+ to enhance 3-hydroxypropionic acid production in Klebsiella pneumoniae , 2020, Biotechnology letters.

[21]  Peng Zhao,et al.  Development of orthogonal T7 expression system in Klebsiella pneumoniae , 2020, Biotechnology and bioengineering.

[22]  Xuefeng Lu,et al.  Engineering cyanobacteria chassis cells toward more efficient photosynthesis. , 2020, Current opinion in biotechnology.

[23]  Tong Un Chae,et al.  High‐level production of 3‐hydroxypropionic acid from glycerol as a sole carbon source using metabolically engineered Escherichia coli , 2020, Biotechnology and bioengineering.

[24]  Sunghoon Park,et al.  Use of acetate for the production of 3-hydroxypropionic acid by metabolically-engineered Pseudomonas denitrificans. , 2020, Bioresource technology.

[25]  Jeong-Geol Na,et al.  Metabolic engineering of type II methanotroph, Methylosinus trichosporium OB3b, for production of 3-hydroxypropionic acid from methane via a malonyl-CoA reductase-dependent pathway. , 2020, Metabolic engineering.

[26]  W. Dai,et al.  Engineering Corynebacterium glutamicum for the Efficient Production of 3-Hydroxypropionic Acid from a Mixture of Glucose and Acetate via the Malonyl-CoA Pathway , 2020, Catalysts.

[27]  Hyo Jin Kim,et al.  Improved production of 3-hydroxypropionic acid in engineered Escherichia coli by rebalancing heterologous and endogenous synthetic pathways. , 2019, Bioresource technology.

[28]  Tao Wang,et al.  Screening, identification, and low‐energy ion modified breeding of a yeast strain producing high level of 3‐hydroxypropionic acid , 2019, MicrobiologyOpen.

[29]  Guannan Sun,et al.  Production of 3-hydroxypropionate using a novel malonyl-CoA-mediated biosynthetic pathway in genetically engineeredE. colistrain , 2019, Green Chemistry.

[30]  Hyo Jin Kim,et al.  Enhanced production of 3-hydroxypropionic acid from glucose and xylose by alleviation of metabolic congestion due to glycerol flux in engineered Escherichia coli. , 2019, Bioresource technology.

[31]  I. Mijakovic,et al.  Production of 3-Hydroxypropanoic Acid From Glycerol by Metabolically Engineered Bacteria , 2019, Front. Bioeng. Biotechnol..

[32]  J. R. Kim,et al.  Development of 3-hydroxypropionic-acid-tolerant strain of Escherichia coli W and role of minor global regulator yieP. , 2019, Metabolic engineering.

[33]  Peng Zhao,et al.  Exploiting tandem repetitive promoters for high-level production of 3-hydroxypropionic acid , 2019, Applied Microbiology and Biotechnology.

[34]  J. Keasling,et al.  Exploring small-scale chemostats to scale up microbial processes: 3-hydroxypropionic acid production in S. cerevisiae , 2019, Microbial Cell Factories.

[35]  Yanhe Ma,et al.  Efficient production of 3-hydroxypropionate from fatty acids feedstock in Escherichia coli. , 2019, Metabolic engineering.

[36]  A. Kondo,et al.  Enhancing 3-hydroxypropionic acid production in combination with sugar supply engineering by cell surface-display and metabolic engineering of Schizosaccharomyces pombe , 2018, Microbial Cell Factories.

[37]  G. Jung,et al.  Efficient Conversion of Acetate to 3-Hydroxypropionic Acid by Engineered Escherichia coli , 2018, Catalysts.

[38]  D. Wei,et al.  Identification of the enzymes responsible for 3-hydroxypropionic acid formation and their use in improving 3-hydroxypropionic acid production in Gluconobacter oxydans DSM 2003. , 2018, Bioresource technology.

[39]  Bing Huang,et al.  Efficient 3-hydroxypropionic acid production from glycerol by metabolically engineered Klebsiella pneumoniae , 2018, Bioresources and Bioprocessing.

[40]  Florence de Fouchécour,et al.  Process engineering for microbial production of 3-hydroxypropionic acid. , 2018, Biotechnology advances.

[41]  U. Rova,et al.  Biological Production of 3-Hydroxypropionic Acid: An Update on the Current Status , 2018 .

[42]  E. Seol,et al.  Metabolic engineering of Klebsiella pneumoniae J2B for co-production of 3-hydroxypropionic acid and 1,3-propanediol from glycerol: Reduction of acetate and other by-products. , 2017, Bioresource technology.

[43]  Vinod Kumar,et al.  Potential and limitations of Klebsiella pneumoniae as a microbial cell factory utilizing glycerol as the carbon source. , 2017, Biotechnology advances.

[44]  G. Jung,et al.  Production of 3-hydroxypropionic acid by balancing the pathway enzymes using synthetic cassette architecture. , 2017, Journal of biotechnology.

[45]  K. Takegawa,et al.  Production of 3-hydroxypropionic acid via the malonyl-CoA pathway using recombinant fission yeast strains. , 2017, Journal of bioscience and bioengineering.

[46]  I. Michie,et al.  Anodic electro-fermentation of 3-hydroxypropionic acid from glycerol by recombinant Klebsiella pneumoniae L17 in a bioelectrochemical system , 2017, Biotechnology for Biofuels.

[47]  Zhi-Qiang Liu,et al.  3‐Hydroxypropionic acid production by recombinant Escherichia coli ZJU‐3HP01 using glycerol–glucose dual‐substrate fermentative strategy , 2017, Biotechnology and applied biochemistry.

[48]  P. Tian,et al.  Production of 1,3-propanediol from glycerol using a new isolate Klebsiella sp. AA405 carrying low levels of virulence factors , 2017 .

[49]  Zhenghong Xu,et al.  Nitrile-hydrolyzing enzyme from Meyerozyma guilliermondii and its potential in biosynthesis of 3-hydroxypropionic acid , 2017, Bioprocess and Biosystems Engineering.

[50]  A. Goelzer,et al.  Conversion of Glycerol to 3-Hydroxypropanoic Acid by Genetically Engineered Bacillus subtilis , 2017, Front. Microbiol..

[51]  Yu Shen,et al.  Increasing Malonyl-CoA Derived Product through Controlling the Transcription Regulators of Phospholipid Synthesis in Saccharomyces cerevisiae. , 2017, ACS synthetic biology.

[52]  B. Mattiasson,et al.  Crosslinked, cryostructured Lactobacillus reuteri monoliths for production of 3-hydroxypropionaldehyde, 3-hydroxypropionic acid and 1,3-propanediol from glycerol. , 2017, Journal of biotechnology.

[53]  박성훈,et al.  Promoter system inducing expression by 3-hydroxypropionic acid and method for biological production of 3-hydroxypropionic acid using same , 2016 .

[54]  Ying Li,et al.  High Production of 3-Hydroxypropionic Acid in Klebsiella pneumoniae by Systematic Optimization of Glycerol Metabolism , 2016, Scientific Reports.

[55]  G. Jung,et al.  Optimum Rebalancing of the 3-Hydroxypropionic Acid Production Pathway from Glycerol in Escherichia coli. , 2016, ACS synthetic biology.

[56]  Lars M. Blank,et al.  Engineering and systems-level analysis of Saccharomyces cerevisiae for production of 3-hydroxypropionic acid via malonyl-CoA reductase-dependent pathway , 2016, Microbial Cell Factories.

[57]  Sang Yup Lee,et al.  Metabolic Engineering of Escherichia coli for the Production of 3-Hydroxypropionic Acid and Malonic Acid through β-Alanine Route. , 2016, ACS synthetic biology.

[58]  M. Xian,et al.  Functional balance between enzymes in malonyl-CoA pathway for 3-hydroxypropionate biosynthesis. , 2016, Metabolic engineering.

[59]  Lei Chen,et al.  Biosynthesis of platform chemical 3-hydroxypropionic acid (3-HP) directly from CO2 in cyanobacterium Synechocystis sp. PCC 6803. , 2016, Metabolic engineering.

[60]  Zhimin Li,et al.  Transcriptional Regulation of Genes Involved in 3-Hydroxypropionic Acid Production in Response to Aeration of Recombinant Klebsiella pneumoniae , 2016, Applied Biochemistry and Biotechnology.

[61]  R. Hatti-Kaul,et al.  Bio-based 3-hydroxypropionic- and acrylic acid production from biodiesel glycerol via integrated microbial and chemical catalysis , 2015, Microbial Cell Factories.

[62]  Jin-Ho Seo,et al.  Simultaneous conversion of glucose and xylose to 3-hydroxypropionic acid in engineered Escherichia coli by modulation of sugar transport and glycerol synthesis. , 2015, Bioresource technology.

[63]  E. Seol,et al.  Deletion of putative oxidoreductases from Klebsiella pneumoniae J2B could reduce 1,3-propanediol during the production of 3-hydroxypropionic acid from glycerol , 2015, Biotechnology and Bioprocess Engineering.

[64]  J. Nielsen,et al.  Production of 3-hydroxypropionic acid from glucose and xylose by metabolically engineered Saccharomyces cerevisiae , 2015, Metabolic engineering communications.

[65]  D. Wei,et al.  Development of a two-step process for production of 3-hydroxypropionic acid from glycerol using Klebsiella pneumoniae and Gluconobacter oxydans , 2015, Bioprocess and Biosystems Engineering.

[66]  Taizo Hanai,et al.  Enhancement of 3-hydroxypropionic acid production from glycerol by using a metabolic toggle switch , 2015, Microbial Cell Factories.

[67]  James C Liao,et al.  Metabolic engineering of cyanobacteria for photosynthetic 3-hydroxypropionic acid production from CO2 using Synechococcus elongatus PCC 7942. , 2015, Metabolic engineering.

[68]  S. Lee,et al.  Metabolic engineering of Escherichia coli for the production of 3-aminopropionic acid. , 2015, Metabolic engineering.

[69]  Robert J Linhardt,et al.  Regulating malonyl-CoA metabolism via synthetic antisense RNAs for enhanced biosynthesis of natural products. , 2015, Metabolic engineering.

[70]  Javier A. Linares-Pastén,et al.  Production of 3-hydroxypropionic acid from 3-hydroxypropionaldehyde by recombinant Escherichia coli co-expressing Lactobacillus reuteri propanediol utilization enzymes. , 2015, Bioresource technology.

[71]  Young Soo Kim,et al.  Metabolic engineering of 3‐hydroxypropionic acid biosynthesis in Escherichia coli , 2015, Biotechnology and bioengineering.

[72]  Guoqiang Chen,et al.  Engineering Halomonas TD01 for the low-cost production of polyhydroxyalkanoates. , 2014, Metabolic engineering.

[73]  Nikolaus Sonnenschein,et al.  Evolution reveals a glutathione-dependent mechanism of 3-hydroxypropionic acid tolerance. , 2014, Metabolic engineering.

[74]  R. Britton,et al.  Flux analysis of the Lactobacillus reuteri propanediol-utilization pathway for production of 3-hydroxypropionaldehyde, 3-hydroxypropionic acid and 1,3-propanediol from glycerol , 2014, Microbial Cell Factories.

[75]  Jens Nielsen,et al.  Improving Production of Malonyl Coenzyme A-Derived Metabolites by Abolishing Snf1-Dependent Regulation of Acc1 , 2014, mBio.

[76]  Won Seok Jung,et al.  Elevated production of 3-hydroxypropionic acid by metabolic engineering of the glycerol metabolism in Escherichia coli. , 2014, Metabolic engineering.

[77]  Jin-Ho Seo,et al.  Enhanced production of 3-hydroxypropionic acid from glycerol by modulation of glycerol metabolism in recombinant Escherichia coli. , 2014, Bioresource technology.

[78]  Chelladurai Rathnasingh,et al.  Production of 3‐hydroxypropionic acid from glycerol by recombinant Pseudomonas denitrificans , 2013, Biotechnology and bioengineering.

[79]  Vinod Kumar,et al.  Recent advances in biological production of 3-hydroxypropionic acid. , 2013, Biotechnology advances.

[80]  H. Amin,et al.  1,2 Propanediol utilization by Lactobacillus reuteri DSM 20016, role in bioconversion of glycerol to 1,3 propanediol, 3-hydroxypropionaldehyde and 3-hydroxypropionic acid , 2013 .

[81]  Vinod Kumar,et al.  Production of 3‐hydroxypropionic acid from glycerol by recombinant Klebsiella pneumoniae ΔdhaTΔyqhD which can produce vitamin B12 naturally , 2013, Biotechnology and bioengineering.

[82]  젠센 홀리,et al.  Compositions and methods for 3-hydroxypropionic acid production , 2011 .

[83]  Joseph J. Bozell,et al.  Technology development for the production of biobased products from biorefinery carbohydrates—the US Department of Energy’s “Top 10” revisited , 2010 .

[84]  M. Prentice,et al.  Lactobacillus reuteri DSM 20016 Produces Cobalamin-Dependent Diol Dehydratase in Metabolosomes and Metabolizes 1,2-Propanediol by Disproportionation , 2008, Journal of bacteriology.

[85]  Johnathan E. Holladay,et al.  Top Value Added Chemicals From Biomass. Volume 1 - Results of Screening for Potential Candidates From Sugars and Synthesis Gas , 2004 .

[86]  W. Eisenreich,et al.  Retrobiosynthetic analysis of carbon fixation in the phototrophic eubacterium Chloroflexus aurantiacus. , 1993, European journal of biochemistry.

[87]  L. Axelsson,et al.  Utilization of Glycerol as a Hydrogen Acceptor by Lactobacillus reuteri: Purification of 1,3-Propanediol:NAD+ Oxidoreductase , 1990, Applied and environmental microbiology.

[88]  I. Casas,et al.  Production and isolation of reuterin, a growth inhibitor produced by Lactobacillus reuteri , 1988, Antimicrobial Agents and Chemotherapy.

[89]  Liming Liu,et al.  A biosynthesis pathway for 3-hydroxypropionic acid production in genetically engineered Saccharomyces cerevisiae , 2021, Green Chemistry.

[90]  De-hua Liu,et al.  Metabolic engineering of Corynebacterium glutamicum for the production of 3-hydroxypropionic acid from glucose and xylose. , 2017, Metabolic engineering.

[91]  Jens Nielsen,et al.  Establishing a synthetic pathway for high-level production of 3-hydroxypropionic acid in Saccharomyces cerevisiae via β-alanine. , 2015, Metabolic engineering.

[92]  Vinod Kumar,et al.  Effect of puuC overexpression and nitrate addition on glycerol metabolism and anaerobic 3-hydroxypropionic acid production in recombinant Klebsiella pneumoniae ΔglpKΔdhaT. , 2013, Metabolic engineering.

[93]  Hongjuan Liu,et al.  Multiple growth inhibition of Klebsiella pneumoniae in 1,3-propanediol fermentation , 2004, Biotechnology Letters.