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Metabolic engineering of Escherichia coli for (2S)-pinocembrin production from glucose by a modular metabolic strategy

Paper ID Volume ID Publish Year Pages File Format Full-Text
31593 44823 2013 8 PDF Available
Title
Metabolic engineering of Escherichia coli for (2S)-pinocembrin production from glucose by a modular metabolic strategy
Abstract

Flavonoids are valuable natural products widely used in human health and nutrition. Recent advances in synthetic biology and metabolic engineering have yielded improved strain titers and yields. However, current fermentation strategies often require supplementation of expensive phenylpropanoic precursors in the media and separate evaluation of each strategy in turn as part of the flavonoid pathway, implicitly assuming the modifications are additive. In this study, an Escherichia coli fermentation system was developed to bypass both of these problems. An eight-step pathway, consisting of 3-deoxy-d-arabinoheptulosonate-7-phosphate synthase (DAHPS), chorismate mutase/prephenate dehydratase (CM/PDT), phenylalanine ammonia lyase (PAL), 4-coumarate:CoA ligase (4CL), chalcone synthase (CHS), chalcone isomerase (CHI), malonate synthetase, and malonate carrier protein, was assembled on four vectors in order to produce the flavonoid precursor (2S)-pinocembrin directly from glucose. Furthermore, a modular metabolic strategy was employed to identify conditions that optimally balance the four pathway modules. Once this metabolic balance was achieved, such strains were capable of producing 40.02 mg/L (2S)-pinocembrin directly from glucose. These results were attained by culturing engineered cells in minimal medium without additional precursor supplementation. The fermentation platform described here paves the way for the development of an economical process for microbial production of flavonoids directly from glucose.

graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► The flavonoid precursor (2S)-pinocembrin was produced directly from glucose. ► A modular metabolic strategy was employed to balance the overall pathway. ► Metabolic burden from four plasmids and expression of genes was alleviated.

Keywords
Escherichia coli; Flavonoids; Metabolic engineering; (2S)-pinocembrin
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Publisher
Database: Elsevier - ScienceDirect
Journal: Metabolic Engineering - Volume 16, March 2013, Pages 48–55
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