Journal article

Genome-Mining-Guided Discovery and Characterization of the PKS-NRPS-Hybrid Polyoxyperuin Produced by a Marine-Derived Streptomycete


Authors listKresna, IDM; Wuisan, ZG; Pohl, JM; Mettal, U; Linares-Otoya, V; Gand, M; Marner, M; Linares-Otoya, L; Böhringer, N; Vilcinskas, A; Schäberle, TF

Publication year2022

Pages888-898

JournalJournal of Natural Products

Volume number85

Issue number4

DOI Linkhttps://doi.org/10.1021/acs.jnatprod.1c01018

PublisherAmerican Chemical Society


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.




Citation Styles

Harvard Citation styleKresna, I., Wuisan, Z., Pohl, J., Mettal, U., Linares-Otoya, V., Gand, M., et al. (2022) Genome-Mining-Guided Discovery and Characterization of the PKS-NRPS-Hybrid Polyoxyperuin Produced by a Marine-Derived Streptomycete, Journal of Natural Products, 85(4), pp. 888-898. https://doi.org/10.1021/acs.jnatprod.1c01018

APA Citation styleKresna, I., Wuisan, Z., Pohl, J., Mettal, U., Linares-Otoya, V., Gand, M., Marner, M., Linares-Otoya, L., Böhringer, N., Vilcinskas, A., & Schäberle, T. (2022). Genome-Mining-Guided Discovery and Characterization of the PKS-NRPS-Hybrid Polyoxyperuin Produced by a Marine-Derived Streptomycete. Journal of Natural Products. 85(4), 888-898. https://doi.org/10.1021/acs.jnatprod.1c01018


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