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Production improvement of FK506 in Streptomyces tsukubaensis by metabolic engineering strategy. | LitMetric

Production improvement of FK506 in Streptomyces tsukubaensis by metabolic engineering strategy.

J Appl Microbiol

First Affiliated Hospital and Institute of Pharmaceutical Biotechnology, Zhejiang University School of Medicine, Hangzhou 310058, China.

Published: July 2023

AI Article Synopsis

Article Abstract

Aims: Study of the effect of isoleucine on the biosynthesis of FK506 and modification of its producing strain to improve the production of FK506.

Methods And Results: Metabolomics analysis was conducted to explore key changes in the metabolic processes of Streptomyces tsukubaensis Δ68 in medium with and without isoleucine. In-depth analysis revealed that the shikimate pathway, methylmalonyl-CoA, and pyruvate might be the rate-limiting factors in FK506 biosynthesis. Overexpression of involved gene PCCB1 in S. tsukubaensis Δ68, a high-yielding strain Δ68-PCCB1 was generated. Additionally, the amino acids supplement was further optimized to improve FK506 biosynthesis. Finally, FK506 production was increased to 929.6 mg L-1, which was 56.6% higher than that in the starter strain, when supplemented isoleucine and valine at 9 and 4 g L-1, respectively.

Conclusions: Methylmalonyl-CoA might be the key rate-limiting factors in FK506 biosynthesis and overexpression of the gene PCCB1 and further addition of isoleucine and valine could increase the yield of FK506 by 56.6%.

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Source
http://dx.doi.org/10.1093/jambio/lxad142DOI Listing

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