Abstract

A new 14-membered homodimeric macrodiolide, brevidiolide (3), along with four known aromatic compounds (1, 2, 4 and 5) were obtained by heterologous expression of the recombinant plasmid pWLI823 expressing the G231L variant of VioA in the marine-derived Brevibacterium sp. 7002-073. The structures of 1–5 were elucidated on the basis of LC-MS and 2D NMR spectroscopic analyses. In the evaluation for the antibacterial activities of the compounds against multi-drug resistant (MDR) strains, 5 showed notable growth inhibition against Staphylococcus aureus CCARM 3090 and Klebsiella pneumoniae ATCC 13883, with a minimum inhibitory concentration (MIC) value of 3.12 µg/mL.

Highlights

  • Marine-derived actinomycetes, with their extreme living environment featuring low temperatures and high pressure as well as poor nutrient availability, are considered to have great potential to generate structurally novel and biologically active secondary metabolites [1,2]

  • Small molecules produced by a microbe may act as signal molecules to regulate gene expression in other microbes depending on the treating concentration [7], triggering the production of related compounds in the heterologous hosts

  • We identified a series of antibiotic violapyrone derivatives, which are encoded by the type III polyketide synthetase VioA, from deep sea-derived Streptomyces somaliansis

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Summary

Introduction

Marine-derived actinomycetes, with their extreme living environment featuring low temperatures and high pressure as well as poor nutrient availability, are considered to have great potential to generate structurally novel and biologically active secondary metabolites [1,2]. The actinomycete-derived compounds reported to date are just the tip of an iceberg: a large number of the molecules are cryptic due to the silent genes [3]. Activating the silent genes becomes an important key to entering the locked world of inaccessible compounds generated by marine actinomycetes. Since the 1980s, a wide range of approaches have been used to activate/modulate silent genes in microbes [4,5], among which cell-cell communication by signaling molecules has attracted increasing attention [6]. Small molecules produced by a microbe may act as signal molecules to regulate gene expression in other microbes depending on the treating concentration [7], triggering the production of related compounds in the heterologous hosts.

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