Organic Letters
Organic Letters
3 years ago

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

Genome Mining and Activation of a Silent PKS/NRPS Gene Cluster Direct the Production of Totopotensamides
Liujuan Zheng, Qingbo Zhang, Ruidong Chen, Changsheng Zhang, Yiguang Zhu, Huixian Li, Bin Tan
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.

Publisher URL: http://dx.doi.org/10.1021/acs.orglett.7b02878

DOI: 10.1021/acs.orglett.7b02878

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