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The Expression Modulation of the Key Enzyme Acc for Highly Efficient 3-Hydroxypropionic Acid Production

3-Hydroxypropionic acid (3-HP) is a promising high value-added chemical. Acetyl-CoA carboxylase (Acc) is a vital rate-limiting step in 3-HP biosynthesis through the malonyl-CoA pathway. However, Acc toxicity in cells during growth blocks its ability to catalyze acetyl-CoA to malonyl-CoA. The balanci...

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Autores principales: Wang, Sumeng, Jin, Xin, Jiang, Wei, Wang, Qian, Qi, Qingsheng, Liang, Quanfeng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9130761/
https://www.ncbi.nlm.nih.gov/pubmed/35633674
http://dx.doi.org/10.3389/fmicb.2022.902848
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author Wang, Sumeng
Jin, Xin
Jiang, Wei
Wang, Qian
Qi, Qingsheng
Liang, Quanfeng
author_facet Wang, Sumeng
Jin, Xin
Jiang, Wei
Wang, Qian
Qi, Qingsheng
Liang, Quanfeng
author_sort Wang, Sumeng
collection PubMed
description 3-Hydroxypropionic acid (3-HP) is a promising high value-added chemical. Acetyl-CoA carboxylase (Acc) is a vital rate-limiting step in 3-HP biosynthesis through the malonyl-CoA pathway. However, Acc toxicity in cells during growth blocks its ability to catalyze acetyl-CoA to malonyl-CoA. The balancing of Acc and malonyl-CoA reductase (MCR) expression is another an unexplored but key process in 3-HP production. To solve these problems, in the present study, we developed a method to mitigate Acc toxicity cell growth through Acc subunits (AccBC and DtsR1) expression adjustment. The results revealed that cell growth and 3-HP production can be accelerated through the adjustment of DtsR1 and AccBC expression. Subsequently, the balancing Acc and MCR expression was also employed for 3-HP production, the engineered strain achieved the highest titer of 6.8 g/L, with a high yield of 0.566 g/g glucose and productivity of 0.13 g/L/h, in shake-flask fermentation through the malonyl-CoA pathway. Likewise, the engineered strain also had the highest productivity (1.03 g/L/h) as well as a high yield (0.246 g/g glucose) and titer (up to 38.13 g/L) in fed-batch fermentation, constituting the most efficient strain for 3-HP production through the malonyl-CoA pathway using a cheap carbon source. This strategy might facilitate the production of other malonyl-CoA-derived chemical compounds in the future.
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spelling pubmed-91307612022-05-26 The Expression Modulation of the Key Enzyme Acc for Highly Efficient 3-Hydroxypropionic Acid Production Wang, Sumeng Jin, Xin Jiang, Wei Wang, Qian Qi, Qingsheng Liang, Quanfeng Front Microbiol Microbiology 3-Hydroxypropionic acid (3-HP) is a promising high value-added chemical. Acetyl-CoA carboxylase (Acc) is a vital rate-limiting step in 3-HP biosynthesis through the malonyl-CoA pathway. However, Acc toxicity in cells during growth blocks its ability to catalyze acetyl-CoA to malonyl-CoA. The balancing of Acc and malonyl-CoA reductase (MCR) expression is another an unexplored but key process in 3-HP production. To solve these problems, in the present study, we developed a method to mitigate Acc toxicity cell growth through Acc subunits (AccBC and DtsR1) expression adjustment. The results revealed that cell growth and 3-HP production can be accelerated through the adjustment of DtsR1 and AccBC expression. Subsequently, the balancing Acc and MCR expression was also employed for 3-HP production, the engineered strain achieved the highest titer of 6.8 g/L, with a high yield of 0.566 g/g glucose and productivity of 0.13 g/L/h, in shake-flask fermentation through the malonyl-CoA pathway. Likewise, the engineered strain also had the highest productivity (1.03 g/L/h) as well as a high yield (0.246 g/g glucose) and titer (up to 38.13 g/L) in fed-batch fermentation, constituting the most efficient strain for 3-HP production through the malonyl-CoA pathway using a cheap carbon source. This strategy might facilitate the production of other malonyl-CoA-derived chemical compounds in the future. Frontiers Media S.A. 2022-05-11 /pmc/articles/PMC9130761/ /pubmed/35633674 http://dx.doi.org/10.3389/fmicb.2022.902848 Text en Copyright © 2022 Wang, Jin, Jiang, Wang, Qi and Liang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Wang, Sumeng
Jin, Xin
Jiang, Wei
Wang, Qian
Qi, Qingsheng
Liang, Quanfeng
The Expression Modulation of the Key Enzyme Acc for Highly Efficient 3-Hydroxypropionic Acid Production
title The Expression Modulation of the Key Enzyme Acc for Highly Efficient 3-Hydroxypropionic Acid Production
title_full The Expression Modulation of the Key Enzyme Acc for Highly Efficient 3-Hydroxypropionic Acid Production
title_fullStr The Expression Modulation of the Key Enzyme Acc for Highly Efficient 3-Hydroxypropionic Acid Production
title_full_unstemmed The Expression Modulation of the Key Enzyme Acc for Highly Efficient 3-Hydroxypropionic Acid Production
title_short The Expression Modulation of the Key Enzyme Acc for Highly Efficient 3-Hydroxypropionic Acid Production
title_sort expression modulation of the key enzyme acc for highly efficient 3-hydroxypropionic acid production
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9130761/
https://www.ncbi.nlm.nih.gov/pubmed/35633674
http://dx.doi.org/10.3389/fmicb.2022.902848
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