Design and kinetic analysis of a hybrid promoter-regulator system for malonyl-CoA sensing in Escherichia coli

Peng Xu; Wenya Wang; Lingyun Li; Namita Bhan; Fuming Zhang; Mattheos A.G. Koffas

doi:10.1021/cb400623m

Design and kinetic analysis of a hybrid promoter-regulator system for malonyl-CoA sensing in Escherichia coli

Peng Xu, Wenya Wang, Lingyun Li, Namita Bhan, Fuming Zhang, Mattheos A.G. Koffas^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

120 Scopus citations

Abstract

Malonyl-CoA is the rate-limiting precursor involved in the chain elongation reaction of a range of value-added pharmaceuticals and biofuels. Development of malonyl-CoA responsive sensors holds great promise in overcoming critical pathway limitations and optimizing production titers and yields. By incorporating the Bacillus subtilis trans-regulatory protein FapR and the cis-regulatory element fapO, we constructed a hybrid promoter-regulatory system that responds to a broad range of intracellular malonyl-CoA concentrations (from 0.1 to 1.1 nmol/mgDW) in Escherichia coli. Elimination of regulatory protein and nonspecific DNA cross-communication leads to a sensor construct that exhibits malonyl-CoA-dependent linear phase kinetics with increased dynamic response range. The sensors reported in this study could potentially control and optimize carbon flux leading to robust biosynthetic pathways for the production of malonyl-CoA-derived compounds.

Original language	English
Pages (from-to)	451-458
Number of pages	8
Journal	ACS Chemical Biology
Volume	9
Issue number	2
DOIs	https://doi.org/10.1021/cb400623m
State	Published - 21 Feb 2014
Externally published	Yes

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abstract = "Malonyl-CoA is the rate-limiting precursor involved in the chain elongation reaction of a range of value-added pharmaceuticals and biofuels. Development of malonyl-CoA responsive sensors holds great promise in overcoming critical pathway limitations and optimizing production titers and yields. By incorporating the Bacillus subtilis trans-regulatory protein FapR and the cis-regulatory element fapO, we constructed a hybrid promoter-regulatory system that responds to a broad range of intracellular malonyl-CoA concentrations (from 0.1 to 1.1 nmol/mgDW) in Escherichia coli. Elimination of regulatory protein and nonspecific DNA cross-communication leads to a sensor construct that exhibits malonyl-CoA-dependent linear phase kinetics with increased dynamic response range. The sensors reported in this study could potentially control and optimize carbon flux leading to robust biosynthetic pathways for the production of malonyl-CoA-derived compounds.",

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AU - Xu, Peng

AU - Wang, Wenya

AU - Li, Lingyun

AU - Bhan, Namita

AU - Zhang, Fuming

AU - Koffas, Mattheos A.G.

PY - 2014/2/21

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AB - Malonyl-CoA is the rate-limiting precursor involved in the chain elongation reaction of a range of value-added pharmaceuticals and biofuels. Development of malonyl-CoA responsive sensors holds great promise in overcoming critical pathway limitations and optimizing production titers and yields. By incorporating the Bacillus subtilis trans-regulatory protein FapR and the cis-regulatory element fapO, we constructed a hybrid promoter-regulatory system that responds to a broad range of intracellular malonyl-CoA concentrations (from 0.1 to 1.1 nmol/mgDW) in Escherichia coli. Elimination of regulatory protein and nonspecific DNA cross-communication leads to a sensor construct that exhibits malonyl-CoA-dependent linear phase kinetics with increased dynamic response range. The sensors reported in this study could potentially control and optimize carbon flux leading to robust biosynthetic pathways for the production of malonyl-CoA-derived compounds.

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Design and kinetic analysis of a hybrid promoter-regulator system for malonyl-CoA sensing in Escherichia coli

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