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- Title
Patchoulol Production with Metabolically Engineered Corynebacterium glutamicum.
- Authors
Henke, Nadja A.; Wichmann, Julian; Baier, Thomas; Frohwitter, Jonas; Lauersen, Kyle J.; Risse, Joe M.; Peters-Wendisch, Petra; Kruse, Olaf; Wendisch, Volker F.
- Abstract
Patchoulol is a sesquiterpene alcohol and an important natural product for the perfume industry. <italic>Corynebacterium glutamicum</italic> 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, <italic>C. glutamicum</italic> 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 <italic>C. glutamicum</italic> strain by applying the following strategies: (i) construction of a farnesyl pyrophosphate-producing platform strain by combining genomic deletions with heterologous expression of <italic>ispA</italic> from <italic>Escherichia coli</italic>; (ii) prevention of carotenoid-like byproduct formation; (iii) overproduction of limiting enzymes from the 2-c-methyl-d-erythritol 4-phosphate (MEP)-pathway to increase precursor supply; and (iv) heterologous expression of the plant patchoulol synthase gene <italic>Pc</italic>PS from <italic>Pogostemon cablin</italic>. 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−1 and volumetric productivities of up to 18 mg L−1 d−1.
- Subjects
CORYNEBACTERIUM; ROBUST statistics; GENOMES; ESCHERICHIA coli; TERPENES
- Publication
Genes, 2018, Vol 9, Issue 4, p219
- ISSN
2073-4425
- Publication type
Article
- DOI
10.3390/genes9040219