Balancing glucose and oxygen uptake rates to enable high amorpha-4,11-diene production in Escherichia coli via the methylerythritol phosphate pathway.

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Tytuł:: Balancing glucose and oxygen uptake rates to enable high amorpha-4,11-diene production in Escherichia coli via the methylerythritol phosphate pathway.
Autorzy:: Patil V; Institute of Biochemical Engineering, University of Stuttgart, Stuttgart, Germany.; Manus Bio, Cambridge, Massachusetts, USA.
Santos CNS; Manus Bio, Cambridge, Massachusetts, USA.
Ajikumar PK; Manus Bio, Cambridge, Massachusetts, USA.
Sarria S; Manus Bio, Cambridge, Massachusetts, USA.
Takors R; Institute of Biochemical Engineering, University of Stuttgart, Stuttgart, Germany.
Źródło:: Biotechnology and bioengineering [Biotechnol Bioeng] 2021 Mar; Vol. 118 (3), pp. 1317-1329. Date of Electronic Publication: 2021 Jan 15.
Typ publikacji:: Journal Article; Research Support, Non-U.S. Gov't
Język:: English
Imprint Name(s):: Publication: <2005->: Hoboken, NJ : Wiley
Original Publication: New York, Wiley.
MeSH Terms:: Oxygen Consumption*
Antimalarials/*metabolism
Erythritol/*analogs & derivatives
Escherichia coli/*metabolism
Glucose/*metabolism
Oxygen/*metabolism
Polycyclic Sesquiterpenes/*metabolism
Sugar Phosphates/*metabolism
Erythritol/metabolism ; Escherichia coli/genetics
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Contributed Indexing:: Keywords: FBA; MEP pathway; NADPH; amorpha-4,11-diene; oxygen uptake; terpenoid
Substance Nomenclature:: 0 (2-C-methylerythritol 4-phosphate)
0 (Antimalarials)
0 (Polycyclic Sesquiterpenes)
0 (Sugar Phosphates)
0 (amorpha-4,11-diene)
IY9XDZ35W2 (Glucose)
RA96B954X6 (Erythritol)
S88TT14065 (Oxygen)
Entry Date(s):: Date Created: 20201217 Date Completed: 20220117 Latest Revision: 20220117
Update Code:: 20240105
DOI:: 10.1002/bit.27655
PMID:: 33331668
: Czasopismo naukowe

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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.
(© 2020 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals LLC.)

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