This title appears in the Scientific Report : 2019 
Modulation of the central carbon metabolism of Corynebacterium glutamicum improves malonyl‐CoA availability and increases plant polyphenol synthesis
Milke, Lars
Ferreira, Patrícia / Kallscheuer, Nicolai / Braga, Adelaide / Vogt, Michael / Kappelmann, Jannick / Oliveira, Joana / Silva, Ana Rita / Rocha, Isabel / Bott, Michael / Noack, Stephan / Faria, Nuno / Marienhagen, Jan (Corresponding author)
Biotechnologie; IBG-1
Biotechnology & bioengineering, 116 (2019) 6, S. 1380 - 1391
New York, NY [u.a.] Wiley 2019
10.1002/bit.26939
30684355
Journal Article
Innovative Synergisms
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Published on 2019-01-26. Available in OpenAccess from 2020-01-26.
Published on 2019-01-26. Available in OpenAccess from 2020-01-26.
Please use the identifier: http://dx.doi.org/10.1002/bit.26939 in citations.
Please use the identifier: http://hdl.handle.net/2128/23488 in citations.

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245 |a Modulation of the central carbon metabolism of Corynebacterium glutamicum improves malonyl‐CoA availability and increases plant polyphenol synthesis 
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520 |a In recent years microorganisms have been engineered towards synthesizing interesting plant polyphenols such as flavonoids and stilbenes from glucose. Currently, the low endogenous supply of malonyl‐CoA, indispensable for plant polyphenol synthesis, impedes high product titers. Usually, limited malonyl‐CoA availability during plant polyphenol production is avoided by supplementing fatty acid synthesis‐inhibiting antibiotics such as cerulenin, which are known to increase the intracellular malonyl‐CoA pool as a side effect. Motivated by the goal of microbial polyphenol synthesis being independent of such expensive additives, we used rational metabolic engineering approaches to modulate regulation of fatty acid synthesis and flux into the tricarboxylic acid cycle (TCA cycle) in Corynebacterium glutamicum strains capable of flavonoid and stilbene synthesis. Initial experiments showed that sole overexpression of genes coding for the native malonyl‐CoA‐forming acetyl‐CoA carboxylase is not sufficient for increasing polyphenol production in C. glutamicum. Hence, the intracellular acetyl‐CoA availability was also increased by reducing the flux into the TCA cycle through reduction of citrate synthase activity. In defined cultivation medium, the constructed C. glutamicum strains accumulated 24 mg·L −1 (0.088 mM) naringenin or 112 mg·L −1 (0.49 mM) resveratrol from glucose without supplementation of phenylpropanoid precursor molecules or any inhibitors of fatty acid synthesis. 
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