期刊
BIOTECHNOLOGY AND BIOENGINEERING
卷 118, 期 3, 页码 1317-1329出版社
WILEY
DOI: 10.1002/bit.27655
关键词
amorpha-4,11-diene; FBA; MEP pathway; NADPH; oxygen uptake; terpenoid
资金
- Manus Bio, Inc.
In this study, key process conditions for producing AMD4,11 in Escherichia coli were optimized, leading to increased carbon flux through the MEP pathway by manipulating glucose uptake rates and oxygen demand. This optimization resulted in a 6.7-fold increase in product titers and a 6.5-fold increase in carbon yield.
Amorpha-4,11-diene (AMD4,11) is a precursor to artemisinin, a potent antimalarial drug that is traditionally extracted from the shrubs of Artemisia annua. Despite significant prior efforts to produce artemisinin and its precursors through biotechnology, there remains a dire need for more efficient biosynthetic routes for its production. Here, we describe the optimization of key process conditions for an Escherichia coli strain producing AMD4,11 via the native methylerythritol phosphate (MEP) pathway. By studying the interplay between glucose uptake rates and oxygen demand, we were able to identify optimal conditions for increasing carbon flux through the MEP pathway by manipulating the availability of NADPH required for terpenoid production. Installation of an optimal q(O2)/q(glucose) led to a 6.7-fold increase in product titers and a 6.5-fold increase in carbon yield.
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