Recent advances, challenges and metabolic engineering strategies in the biosynthesis of 3‐hydroxypropionic acid

Liang, Bo; Sun, Guannan; Nie, Qingjuan; Zhao, Yukun; Jian-ming, Yang

doi:10.1002/bit.28170

Cited by 19 publications

(7 citation statements)

References 236 publications

(422 reference statements)

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“…In the past few years, several industrial parties, such as OPX Biotechnologies, Cargill, Novozymes, and BASF, have developed pilot plants for the bio-based production of 3-HP and its chemical conversion to AA [ 4 , 7 , 8 , 9 ]. A series of genetically engineered microbial cell factories to convert renewable substances into 3-HP have been constructed via different biosynthetic pathways [ 3 , 10 , 11 ]. However, microbial 3-HP synthesis processes still has a certain distance to travel meet the market demand.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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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.

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Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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“…This titer is not high enough for commercial exploitation and a combination of strain and process engineering would be needed to substantially improve titers. Several challenges can be targeted such as preventing buildup of the toxic intermediate 3-hydroxypropanal (3-HPA) as well as byproducts, NAD + co-factor requirement of the aldehyde dehydrogenase, and tolerance to substrate and product ( Liang et al, 2022 ; Zabed et al, 2022 ). Optimization of the production conditions is key to attain the full potential of production strains.…”

Section: Introductionmentioning

confidence: 99%

Engineering Bacillus subtilis for production of 3-hydroxypropanoic acid

Garg

Jers

Hwang

et al. 2023

Front. Bioeng. Biotechnol.

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3-Hydroxypropionic acid (3-HP) is a valuable platform chemical that is used as a precursor for several higher value-added chemical products. There is an increased interest in development of cell factories as a means for the synthesis of 3-HP and various other platform chemicals. For more than a decade, concentrated effort has been invested by the scientific community towards developing bio-based approaches for the production of 3-HP using primarily Escherichia coli and Klebsiella pneumoniae as production hosts. These hosts however might not be optimal for applications in e.g., food industry due primarily to endotoxin production and the pathogenic origin of particularly the K. pneumoniae. We have previously demonstrated that the generally recognized as safe organism Bacillus subtilis can be engineered to produce 3-HP using glycerol, an abundant by-product of the biodiesel industry, as substrate. For commercial exploitation, there is a need to substantially increase the titer. In the present study, we optimized the bioprocess conditions and further engineered the B. subtilis 3-HP production strain. Thereby, using glycerol as substrate, we were able to improve 3-HP production in a 1-L bioreactor to a final titer of 22.9 g/L 3-HP.

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“…3-HP serves as a promising platform chemical to produce various C3-based chemicals, including acrylic acid and its derivatives, which are wildly used in the fields of plastics, pharmaceuticals and agriculture. Extensive studies of 3-HP bioproduction have been performed [ 15 – 17 ] .…”

Section: Introductionmentioning

confidence: 99%

Engineering yeast mitochondrial metabolism for 3-hydroxypropionate production

Zhang

Chen

et al. 2023

Biotechnol Biofuels

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Background With unique physiochemical environments in subcellular organelles, there has been growing interest in harnessing yeast organelles for bioproduct synthesis. Among these organelles, the yeast mitochondrion has been found to be an attractive compartment for production of terpenoids and branched-chain alcohols, which could be credited to the abundant supply of acetyl-CoA, ATP and cofactors. In this study we explored the mitochondrial potential for production of 3-hydroxypropionate (3-HP) and performed the cofactor engineering and flux control at the acetyl-CoA node to maximize 3-HP synthesis. Results Metabolic modeling suggested that the mitochondrion serves as a more suitable compartment for 3-HP synthesis via the malonyl-CoA pathway than the cytosol, due to the opportunity to obtain a higher maximum yield and a lower oxygen consumption. With the malonyl-CoA reductase (MCR) targeted into the mitochondria, the 3-HP production increased to 0.27 g/L compared with 0.09 g/L with MCR expressed in the cytosol. With enhanced expression of dissected MCR enzymes, the titer reached to 4.42 g/L, comparable to the highest titer achieved in the cytosol so far. Then, the mitochondrial NADPH supply was optimized by overexpressing POS5 and IDP1, which resulted in an increase in the 3-HP titer to 5.11 g/L. Furthermore, with induced expression of an ACC1 mutant in the mitochondria, the final 3-HP production reached 6.16 g/L in shake flask fermentations. The constructed strain was then evaluated in fed-batch fermentations, and produced 71.09 g/L 3-HP with a productivity of 0.71 g/L/h and a yield on glucose of 0.23 g/g. Conclusions In this study, the yeast mitochondrion is reported as an attractive compartment for 3-HP production. The final 3-HP titer of 71.09 g/L with a productivity of 0.71 g/L/h was achieved in fed-batch fermentations, representing the highest titer reported for Saccharomyces cerevisiae so far, that demonstrated the potential of recruiting the yeast mitochondria for further development of cell factories.

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Recent advances, challenges and metabolic engineering strategies in the biosynthesis of 3‐hydroxypropionic acid

Cited by 19 publications

References 236 publications

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

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

Engineering Bacillus subtilis for production of 3-hydroxypropanoic acid

Engineering yeast mitochondrial metabolism for 3-hydroxypropionate production

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