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. 2017 Oct 20;19(20):5697-5700.
doi: 10.1021/acs.orglett.7b02878. Epub 2017 Oct 11.

Genome Mining and Activation of a Silent PKS/NRPS Gene Cluster Direct the Production of Totopotensamides

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Genome Mining and Activation of a Silent PKS/NRPS Gene Cluster Direct the Production of Totopotensamides

Ruidong Chen et al. Org Lett. .

Abstract

A 92 kb silent hybrid polyketide and nonribosomal peptide gene cluster in marine-derived Streptomyces pactum SCSIO 02999 was activated by genetically manipulating the regulatory genes, including the knockout of two negative regulators (totR5 and totR3) and overexpression of a positive regulator totR1, to direct the production of the known totopotensamides (TPMs) A (1) and B (3) and a novel sulfonate-containing analogue TPM C (2). Inactivation of totG led to accumulation of TPM B (3) lacking the glycosyl moiety, which indicated TotG as a dedicated glycosyltransferase in the biosynthesis of 1 and 2.

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