1. Genome-Mining-Guided Discovery and Characterization of the PKS-NRPS-Hybrid Polyoxyperuin Produced by a Marine-Derived Streptomycete
- Author
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I Dewa M. Kresna, Zerlina G. Wuisan, Jean-Marie Pohl, Ute Mettal, Virginia Linares Otoya, Martin Gand, Michael Marner, Luis Linares Otoya, Nils Böhringer, Andreas Vilcinskas, Till F. Schäberle, and Publica
- Subjects
Pharmacology ,Complementary and alternative medicine ,Multigene Family ,Organic Chemistry ,Drug Discovery ,Pharmaceutical Science ,Molecular Medicine ,Streptomyces ,Anti-Bacterial Agents ,Analytical Chemistry - Abstract
The azinothricin family comprises several cyclic hexadepsipeptides with diverse pharmacological bioactivities, including antimicrobial, antitumoral, and apoptosis induction. In this work, using a genome mining approach, a biosynthetic gene cluster encoding an azinothricin-like compound was identified from the Streptomyces sp. s120 genome sequence (pop BGC). Comparative MS analysis of extracts from the native producer and a knockout mutant led to the identification of metabolites corresponding to the pop BGC. Furthermore, regulatory elements of the BGC were identified. By overexpression of an LmbU-like transcriptional activator, the production yield of 1 and 2 was increased, enabling isolation and structure elucidation of polyoxyperuin A seco acid (1) and polyoxyperuin A (2) using high-resolution mass spectrometry and NMR spectroscopy. Compound 1 exhibited a low antibiotic effect against Micrococcus luteus, while 2 showed a strong Gram-positive antibiotic effect in a micro-broth-dilution assay.
- Published
- 2022
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