Metabolic Engineering of Yeast for the Production of 3-Hydroxypropionic Acid

Overview

Journal Front Microbiol

Specialty Microbiology

Date 2018 Oct 10

PMID 30298059

Citations 10

Authors

Rong-Yu Ji

Ying Ding

Tian-Qiong Shi

Lu Lin

He Huang

Zhen Gao

Xiao-Jun Ji

Affiliations

Soon will be listed here.

Abstract

The beta-hydroxy acid 3-hydroxypropionic acid (3-HP) is an attractive platform compound that can be used as a precursor for many commercially interesting compounds. In order to reduce the dependence on petroleum and follow sustainable development, 3-HP has been produced biologically from glucose or glycerol. It is reported that 3-HP synthesis pathways can be constructed in microbes such as and the yeast . Among these host strains, yeast is prominent because of its strong acid tolerance which can simplify the fermentation process. Currently, the malonyl-CoA reductase pathway and the β-alanine pathway have been successfully constructed in yeast. This review presents the current developments in 3-HP production using yeast as an industrial host. By combining genome-scale engineering tools, malonyl-CoA biosensors and optimization of downstream fermentation, the production of 3-HP in yeast has the potential to reach or even exceed the yield of chemical production in the future.

Citing Articles

Metabolic engineering of Komagataella phaffii for enhanced 3-hydroxypropionic acid (3-HP) production from methanol.

Avila-Cabre S, Albiol J, Ferrer P J Biol Eng. 2025; 19(1):19.

PMID: 39979934 PMC: 11844118. DOI: 10.1186/s13036-025-00488-x.

Metabolic engineering using acetate as a promising building block for the production of bio-based chemicals.

Gong G, Wu B, Liu L, Li J, Zhu Q, He M Eng Microbiol. 2024; 2(4):100036.

PMID: 39628702 PMC: 11610983. DOI: 10.1016/j.engmic.2022.100036.

Engineering 3-Hydroxypropionic Acid Production from Glucose in through Malonyl-CoA Pathway.

Liu S, Sun Y, Wei T, Gong D, Wang Q, Zhan Z J Fungi (Basel). 2023; 9(5).

PMID: 37233284 PMC: 10219321. DOI: 10.3390/jof9050573.

Schwanniomyces etchellsii, acid-thermotolerant yeasts from urban city soil.

Lertsriwong S, Boonvitthya N, Glinwong C World J Microbiol Biotechnol. 2023; 39(6):159.

PMID: 37067620 DOI: 10.1007/s11274-023-03602-7.

Engineering yeast mitochondrial metabolism for 3-hydroxypropionate production.

Zhang Y, Su M, Chen Y, Wang Z, Nielsen J, Liu Z Biotechnol Biofuels Bioprod. 2023; 16(1):64.

PMID: 37031180 PMC: 10082987. DOI: 10.1186/s13068-023-02309-z.

References

Kocharin K, Chen Y, Siewers V, Nielsen J . Engineering of acetyl-CoA metabolism for the improved production of polyhydroxybutyrate in Saccharomyces cerevisiae. AMB Express. 2012; 2(1):52. PMC: 3519744. DOI: 10.1186/2191-0855-2-52. View

Verho R, Londesborough J, Penttila M, Richard P . Engineering redox cofactor regeneration for improved pentose fermentation in Saccharomyces cerevisiae. Appl Environ Microbiol. 2003; 69(10):5892-7. PMC: 201209. DOI: 10.1128/AEM.69.10.5892-5897.2003. View

Shi S, Chen Y, Siewers V, Nielsen J . Improving production of malonyl coenzyme A-derived metabolites by abolishing Snf1-dependent regulation of Acc1. mBio. 2014; 5(3):e01130-14. PMC: 4010835. DOI: 10.1128/mBio.01130-14. View

Chen Y, Daviet L, Schalk M, Siewers V, Nielsen J . Establishing a platform cell factory through engineering of yeast acetyl-CoA metabolism. Metab Eng. 2012; 15:48-54. DOI: 10.1016/j.ymben.2012.11.002. View

Chen Y, Nielsen J . Biobased organic acids production by metabolically engineered microorganisms. Curr Opin Biotechnol. 2016; 37:165-172. DOI: 10.1016/j.copbio.2015.11.004. View

Chen X, Yang X, Shen Y, Hou J, Bao X . Increasing Malonyl-CoA Derived Product through Controlling the Transcription Regulators of Phospholipid Synthesis in Saccharomyces cerevisiae. ACS Synth Biol. 2017; 6(5):905-912. DOI: 10.1021/acssynbio.6b00346. View

Si T, Luo Y, Bao Z, Zhao H . RNAi-assisted genome evolution in Saccharomyces cerevisiae for complex phenotype engineering. ACS Synth Biol. 2014; 4(3):283-91. DOI: 10.1021/sb500074a. View

Herrmann G, Selmer T, Jessen H, Gokarn R, Selifonova O, Gort S . Two beta-alanyl-CoA:ammonia lyases in Clostridium propionicum. FEBS J. 2005; 272(3):813-21. DOI: 10.1111/j.1742-4658.2004.04518.x. View

Tang X, Lee J, Chen W . Engineering the fatty acid metabolic pathway in for advanced biofuel production. Metab Eng Commun. 2021; 2:58-66. PMC: 8193251. DOI: 10.1016/j.meteno.2015.06.005. View

10.

Guo Z, Zhang L, Ding Z, Shi G . Minimization of glycerol synthesis in industrial ethanol yeast without influencing its fermentation performance. Metab Eng. 2010; 13(1):49-59. DOI: 10.1016/j.ymben.2010.11.003. View

11.

Chen X, Gao C, Guo L, Hu G, Luo Q, Liu J . DCEO Biotechnology: Tools To Design, Construct, Evaluate, and Optimize the Metabolic Pathway for Biosynthesis of Chemicals. Chem Rev. 2017; 118(1):4-72. DOI: 10.1021/acs.chemrev.6b00804. View

12.

Kildegaard K, Jensen N, Schneider K, Czarnotta E, Ozdemir E, Klein T . Engineering and systems-level analysis of Saccharomyces cerevisiae for production of 3-hydroxypropionic acid via malonyl-CoA reductase-dependent pathway. Microb Cell Fact. 2016; 15:53. PMC: 4791802. DOI: 10.1186/s12934-016-0451-5. View

13.

Tehlivets O, Scheuringer K, Kohlwein S . Fatty acid synthesis and elongation in yeast. Biochim Biophys Acta. 2006; 1771(3):255-70. DOI: 10.1016/j.bbalip.2006.07.004. View

14.

Strauss G, Eisenreich W, Bacher A, Fuchs G . 13C-NMR study of autotrophic CO2 fixation pathways in the sulfur-reducing Archaebacterium Thermoproteus neutrophilus and in the phototrophic Eubacterium Chloroflexus aurantiacus. Eur J Biochem. 1992; 205(2):853-66. DOI: 10.1111/j.1432-1033.1992.tb16850.x. View

15.

Chen Y, Siewers V, Nielsen J . Profiling of cytosolic and peroxisomal acetyl-CoA metabolism in Saccharomyces cerevisiae. PLoS One. 2012; 7(8):e42475. PMC: 3411639. DOI: 10.1371/journal.pone.0042475. View

16.

Borodina I, Kildegaard K, Jensen N, Blicher T, Maury J, Sherstyk S . Establishing a synthetic pathway for high-level production of 3-hydroxypropionic acid in Saccharomyces cerevisiae via β-alanine. Metab Eng. 2014; 27:57-64. DOI: 10.1016/j.ymben.2014.10.003. View

17.

Ko Y, Ashok S, Ainala S, Sankaranarayanan M, Chun A, Jung G . Coenzyme B12 can be produced by engineered Escherichia coli under both anaerobic and aerobic conditions. Biotechnol J. 2014; 9(12):1526-35. DOI: 10.1002/biot.201400221. View

18.

Valdehuesa K, Liu H, Nisola G, Chung W, Lee S, Park S . Recent advances in the metabolic engineering of microorganisms for the production of 3-hydroxypropionic acid as C3 platform chemical. Appl Microbiol Biotechnol. 2013; 97(8):3309-21. DOI: 10.1007/s00253-013-4802-4. View

19.

Woods A, Munday M, Scott J, Yang X, Carlson M, Carling D . Yeast SNF1 is functionally related to mammalian AMP-activated protein kinase and regulates acetyl-CoA carboxylase in vivo. J Biol Chem. 1994; 269(30):19509-15. View

20.

Lian J, Si T, Nair N, Zhao H . Design and construction of acetyl-CoA overproducing Saccharomyces cerevisiae strains. Metab Eng. 2014; 24:139-49. DOI: 10.1016/j.ymben.2014.05.010. View