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Balancing glucose and oxygen uptake rates to enable high amorpha‐4,11‐diene production in Escherichia coli via the methylerythritol phosphate pathway
Author(s) -
Patil Vikas,
Santos Christine N. S.,
Ajikumar Parayil K.,
Sarria Stephen,
Takors Ralf
Publication year - 2021
Publication title -
biotechnology and bioengineering
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.136
H-Index - 189
eISSN - 1097-0290
pISSN - 0006-3592
DOI - 10.1002/bit.27655
Subject(s) - artemisia annua , artemisinin , escherichia coli , biochemistry , chemistry , phosphate , metabolic engineering , reactive oxygen species , glucose uptake , biology , microbiology and biotechnology , plasmodium falciparum , enzyme , gene , malaria , insulin , immunology
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.