Mining Indonesian Microbial Biodiversity for Novel Natural Compounds by a Combined Genome Mining and Molecular Networking Approach.

Ira Handayani,Saefuddin Aziz,Yvonne Mast,Hamada Saad,Puspita Lisdiyanti,Nadine Ziemert,Janina Krause,Wien Kusharyoto,Wolfgang Wohlleben,Andreas Kulik,Harald Gross,Athina Gavriilidou,Shanti Ratnakomala

doi:10.3390/md19060316

Abstract

Indonesia is one of the most biodiverse countries in the world and a promising resource for novel natural compound producers. Actinomycetes produce about two thirds of all clinically used antibiotics. Thus, exploiting Indonesia’s microbial diversity for actinomycetes may lead to the discovery of novel antibiotics. A total of 422 actinomycete strains were isolated from three different unique areas in Indonesia and tested for their antimicrobial activity. Nine potent bioactive strains were prioritized for further drug screening approaches. The nine strains were cultivated in different solid and liquid media, and a combination of genome mining analysis and mass spectrometry (MS)-based molecular networking was employed to identify potential novel compounds. By correlating secondary metabolite gene cluster data with MS-based molecular networking results, we identified several gene cluster-encoded biosynthetic products from the nine strains, including naphthyridinomycin, amicetin, echinomycin, tirandamycin, antimycin, and desferrioxamine B. Moreover, 16 putative ion clusters and numerous gene clusters were detected that could not be associated with any known compound, indicating that the strains can produce novel secondary metabolites. Our results demonstrate that sampling of actinomycetes from unique and biodiversity-rich habitats, such as Indonesia, along with a combination of gene cluster networking and molecular networking approaches, accelerates natural product identification.

Highlights

It is 80 years ago that Selman Waksman and Boyd Woodruff discovered actinomycin from Actinomyces (Streptomyces) antibioticus, which was the first antibiotic that was isolated from an actinomycete [1]
Enggano Island was chosen as a sampling location for terrestrial habitats since it is a pristine island with many endemic species and high biodiversity [53,54], whereas Bali and Lombok Island were selected as sampling sites for marine habitats resulting in 422 strains in total (Table 1)
We report on the isolation of 422 actinomycetes strains from three different unique areas in Indonesia

Summary

Introduction

It is 80 years ago that Selman Waksman and Boyd Woodruff discovered actinomycin from Actinomyces (Streptomyces) antibioticus, which was the first antibiotic that was isolated from an actinomycete [1]. Within the family of Actinomycetales, Streptomyces is the most prominent genus in respect to the production of bioactive secondary metabolites since it is the origin of more than 50% of all clinically useful antibiotics [5]. The intensive screening campaigns of soil-derived streptomycetes yielded many currently recognized drugs, such as the antibacterial substance streptomycin, the antifungal metabolite nystatin, and the anticancer compound doxorubicin during the golden era of antibiotics [6,7]. One of the major problems in antibiotic screening programs, in particular with streptomycetes, is the high rediscovery rate of already-known antibacterial compounds through the classical bioactivity-guided paradigms [3]

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