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Improving cellular malonyl-CoA level in Escherichia coli via metabolic engineering

Paper ID Volume ID Publish Year Pages File Format Full-Text
31918 44852 2009 7 PDF Available
Title
Improving cellular malonyl-CoA level in Escherichia coli via metabolic engineering
Abstract

Escherichia coli only maintains a small amount of cellular malonyl-CoA, impeding its utility for overproducing natural products such as polyketides and flavonoids. Here, we report the use of various metabolic engineering strategies to redirect the carbon flux inside E. coli to pathways responsible for the generation of malonyl-CoA. Overexpression of acetyl-CoA carboxylase (Acc) resulted in 3-fold increase in cellular malonyl-CoA concentration. More importantly, overexpression of Acc showed a synergistic effect with increased acetyl-CoA availability, which was achieved by deletion of competing pathways leading to the byproducts acetate and ethanol as well as overexpression of an acetate assimilation enzyme. These engineering efforts led to the creation of an E. coli strain with 15-fold elevated cellular malonyl-CoA level. To demonstrate its utility, this engineered E. coli strain was used to produce an important polyketide, phloroglucinol, and showed near 4-fold higher titer compared with wild-type E. coli, despite the toxicity of phloroglucinol to cell growth. This engineered E. coli strain with elevated cellular malonyl-CoA level should be highly useful for improved production of important natural products where the cellular malonyl-CoA level is rate-limiting.

Keywords
Malonyl-CoA; Metabolic engineering; Polyketides; Flavonoids; Type III polyketide synthases
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Improving cellular malonyl-CoA level in Escherichia coli via metabolic engineering
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Publisher
Database: Elsevier - ScienceDirect
Journal: Metabolic Engineering - Volume 11, Issue 3, May 2009, Pages 192–198
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
Don't Miss Today's Special Offer
Price was $35.95
You save - $31
Price after discount Only $4.95
100% Money Back Guarantee
Full-text PDF Download
Online Support
Any Questions? feel free to contact us