Engineering a short, aldolase based pathway for (R)-1,3-butanediol production in Escherichia coli

Allbwn ymchwil: Cyfraniad at gyfnodolynErthygladolygiad gan gymheiriaid

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Engineering a short, aldolase based pathway for (R)-1,3-butanediol production in Escherichia coli. / Nemr, Kayla; Muller, Jonas; Joo, Jeong Chan et al.
Yn: Metabolic Engineering, Cyfrol 48, 01.07.2018, t. 13-24.

Allbwn ymchwil: Cyfraniad at gyfnodolynErthygladolygiad gan gymheiriaid

HarvardHarvard

Nemr, K, Muller, J, Joo, JC, Gawand, P, Cjoudhary, R, Mendonca, B, Lu, S, Yu, X, Yakunin, A & Mahadevan, R 2018, 'Engineering a short, aldolase based pathway for (R)-1,3-butanediol production in Escherichia coli', Metabolic Engineering, cyfrol. 48, tt. 13-24. https://doi.org/10.1016/j.ymben.2018.04.013

APA

Nemr, K., Muller, J., Joo, J. C., Gawand, P., Cjoudhary, R., Mendonca, B., Lu, S., Yu, X., Yakunin, A., & Mahadevan, R. (2018). Engineering a short, aldolase based pathway for (R)-1,3-butanediol production in Escherichia coli. Metabolic Engineering, 48, 13-24. https://doi.org/10.1016/j.ymben.2018.04.013

CBE

Nemr K, Muller J, Joo JC, Gawand P, Cjoudhary R, Mendonca B, Lu S, Yu X, Yakunin A, Mahadevan R. 2018. Engineering a short, aldolase based pathway for (R)-1,3-butanediol production in Escherichia coli. Metabolic Engineering. 48:13-24. https://doi.org/10.1016/j.ymben.2018.04.013

MLA

VancouverVancouver

Nemr K, Muller J, Joo JC, Gawand P, Cjoudhary R, Mendonca B et al. Engineering a short, aldolase based pathway for (R)-1,3-butanediol production in Escherichia coli. Metabolic Engineering. 2018 Gor 1;48:13-24. Epub 2018 Mai 9. doi: 10.1016/j.ymben.2018.04.013

Author

Nemr, Kayla ; Muller, Jonas ; Joo, Jeong Chan et al. / Engineering a short, aldolase based pathway for (R)-1,3-butanediol production in Escherichia coli. Yn: Metabolic Engineering. 2018 ; Cyfrol 48. tt. 13-24.

RIS

TY - JOUR

T1 - Engineering a short, aldolase based pathway for (R)-1,3-butanediol production in Escherichia coli

AU - Nemr, Kayla

AU - Muller, Jonas

AU - Joo, Jeong Chan

AU - Gawand, Pratish

AU - Cjoudhary, Ruhi

AU - Mendonca, Burton

AU - Lu, Shuyi

AU - Yu, Xiuyan

AU - Yakunin, Alexander

AU - Mahadevan, Radhakrishnan

PY - 2018/7/1

Y1 - 2018/7/1

N2 - Microbial processes can produce a wide range of compounds; however, producing complex and long chain hydrocarbons remains a challenge. Aldol condensation offers a direct route to synthesize these challenging chemistries and can be catalyzed by microbes using aldolases. Deoxyribose-5-phosphate aldolase (DERA) condensesaldehydes and/or ketones to beta-hydroxyaldehydes, which can be further converted to value-added chemicals such as a precursor to cholesterol-lowering drugs. Here, we implement a short, aldolase-based pathway in Escherichia coli to produce (R)-1,3-BDO from glucose, an essential component of pharmaceutical products and cosmetics. First, we expressed a three step heterologous pathway from pyruvate to produce 0.3 g/L of (R)-1,3-BDO with a yield of 11.2 mg/g of glucose in wild-type E. coli K12 MG1655. We used a systems metabolic engineering approach to improve (R)-1,3-BDO titer and yield by: 1) identifying and reducing major by-products: ethanol, acetoin, and 2,3-butanediol; 2) increasing pathway flux through DERA to reduce accumulation of toxic acetaldehyde. We then implemented a two stage fermentation process to improve (R)-1,3-BDO titer by 8-fold to 2.4 g/L and yield by 5-fold to 56 mg/g of glucose (11% of maximum theoretical yield), by controlling pH to 7 and higher dissolved oxygen level. Furthermore, this study highlights the potential of the aldolase chemistry to synthesize diverse products directly from renewable resources in microbes.

AB - Microbial processes can produce a wide range of compounds; however, producing complex and long chain hydrocarbons remains a challenge. Aldol condensation offers a direct route to synthesize these challenging chemistries and can be catalyzed by microbes using aldolases. Deoxyribose-5-phosphate aldolase (DERA) condensesaldehydes and/or ketones to beta-hydroxyaldehydes, which can be further converted to value-added chemicals such as a precursor to cholesterol-lowering drugs. Here, we implement a short, aldolase-based pathway in Escherichia coli to produce (R)-1,3-BDO from glucose, an essential component of pharmaceutical products and cosmetics. First, we expressed a three step heterologous pathway from pyruvate to produce 0.3 g/L of (R)-1,3-BDO with a yield of 11.2 mg/g of glucose in wild-type E. coli K12 MG1655. We used a systems metabolic engineering approach to improve (R)-1,3-BDO titer and yield by: 1) identifying and reducing major by-products: ethanol, acetoin, and 2,3-butanediol; 2) increasing pathway flux through DERA to reduce accumulation of toxic acetaldehyde. We then implemented a two stage fermentation process to improve (R)-1,3-BDO titer by 8-fold to 2.4 g/L and yield by 5-fold to 56 mg/g of glucose (11% of maximum theoretical yield), by controlling pH to 7 and higher dissolved oxygen level. Furthermore, this study highlights the potential of the aldolase chemistry to synthesize diverse products directly from renewable resources in microbes.

U2 - 10.1016/j.ymben.2018.04.013

DO - 10.1016/j.ymben.2018.04.013

M3 - Article

VL - 48

SP - 13

EP - 24

JO - Metabolic Engineering

JF - Metabolic Engineering

ER -