New natural products identified by combined genomics-metabolomics profiling of marine Streptomyces sp. MP131-18

Constanze Paulus,Stefan Zahler,Maksym Myronovskyi,Larisa P Terekhova,Simone Braig,Yuriy Rebets,Sergey B Zotchev,Suvd Nadmid,Bogdan Tokovenko,Andriy Luzhetskyy,Jörn Kalinowski,Christian Rückert

doi:10.1038/srep42382

Abstract

Marine actinobacteria are drawing more and more attention as a promising source of new natural products. Here we report isolation, genome sequencing and metabolic profiling of new strain Streptomyces sp. MP131-18 isolated from marine sediment sample collected in the Trondheim Fjord, Norway. The 16S rRNA and multilocus phylogenetic analysis showed that MP131-18 belongs to the genus Streptomyces. The genome of MP131-18 isolate was sequenced, and 36 gene clusters involved in the biosynthesis of 18 different types of secondary metabolites were predicted using antiSMASH analysis. The combined genomics-metabolics profiling of the strain led to the identification of several new biologically active compounds. As a result, the family of bisindole pyrroles spiroindimicins was extended with two new members, spiroindimicins E and F. Furthermore, prediction of the biosynthetic pathway for unusual α-pyrone lagunapyrone isolated from MP131-18 resulted in foresight and identification of two new compounds of this family – lagunapyrones D and E. The diversity of identified and predicted compounds from Streptomyces sp. MP131-18 demonstrates that marine-derived actinomycetes are not only a promising source of new natural products, but also represent a valuable pool of genes for combinatorial biosynthesis of secondary metabolites.

Highlights

The discovery of new antibiotics remains one of the most important tasks of modern biotechnology due to the rapid emergence of antibiotic resistance among pathogenic bacteria[1]
The sediment suspension from which this isolate was obtained was treated with extremely high frequency radiation (EHF) that was shown to selectively promote growth of various rare actinomycete bacteria[18]
A 1421 bp PCR fragment obtained from the genomic DNA of MP131-18, representing the almost complete 16S rRNA gene, was sequenced and analysed using Ribosomal Database Project Classifier, which strongly suggested it belonging to the genus Streptomyces

Summary

Introduction

The discovery of new antibiotics remains one of the most important tasks of modern biotechnology due to the rapid emergence of antibiotic resistance among pathogenic bacteria[1] The latter leads to an increasing number of untreatable or poorly treatable bacterial infections, which can potentially become one of the leading causes of mortality[2]. The post-genomic era in actinomycete research is outlined by the discovery of multiple secondary metabolite biosynthesis gene clusters in the strains thought to be producing only few compounds[12,13] This finding led to a rapid development of genomics-based approaches for the discovery of new natural products, resulting in isolation of new secondary metabolites from well-studied strains[14,15]. The application of genomics-based approaches has broadened the diversity of natural products discovered from the marine actinomycetes[16,17]

Methods

Results

Conclusion