BioChem - DOS

Patchoulol production with metabolically engineered Corynebacterium glutamicum

Genes

Henke, Nadja A.; Wichmann, Julian; Baier, Thomas; Frohwitter, Jonas; Lauersen, Kyle J.; Risse, Joe M.; Peters-Wendisch, Petra; Kruse, Olaf; Wendisch, Volker F.

<P>Patchoulol is a sesquiterpene alcohol and an important natural product for the perfume industry. <I>Corynebacterium glutamicum</I> is the prominent host for the fermentative production of amino acids with an average annual production volume of ~6 million tons. Due to its robustness and well established large-scale fermentation, <I>C. glutamicum</I> has been engineered for the production of a number of value-added compounds including terpenoids. Both C40 and C50 carotenoids, including the industrially relevant astaxanthin, and short-chain terpenes such as the sesquiterpene valencene can be produced with this organism. In this study, systematic metabolic engineering enabled construction of a patchoulol producing <I>C. glutamicum</I> strain by applying the following strategies: (i) construction of a farnesyl pyrophosphate-producing platform strain by combining genomic deletions with heterologous expression of <I>ispA</I> from <I>Escherichia coli</I>; (ii) prevention of carotenoid-like byproduct formation; (iii) overproduction of limiting enzymes from the 2-<SMALL>C</SMALL>-methyl-<SMALL>D</SMALL>-erythritol 4-phosphate (MEP)-pathway to increase precursor supply; and (iv) heterologous expression of the plant patchoulol synthase gene <I>Pc</I>PS from <I>Pogostemon cablin</I>. Additionally, a proof of principle liter-scale fermentation with a two-phase organic overlay-culture medium system for terpenoid capture was performed. To the best of our knowledge, the patchoulol titers demonstrated here are the highest reported to date with up to 60 mg L<SUP>&#x2212;1</SUP> and volumetric productivities of up to 18 mg L<SUP>&#x2212;1</SUP> d<SUP>&#x2212;1</SUP>.</P>

2018

MDPI

cc-by

2073-4425

9

4

pp.219

10.3390/genes9040219

http://click.ndsl.kr/servlet/OpenAPIDetailView?keyValue=05787966&target=NART&cn=NART92226639

https://www.mdpi.com/2073-4425/9/4/219/pdf?version=1525348920

patchoulol; Corynebacterium glutamicum; sesquiterpene; metabolic engineering; algae; Escherichia coli