Abstract
Mangrove-derived actinomycetes are promising sources of bioactive natural products. In this study, using homologous screening of the biosynthetic genes and anti-microorganism/tumor assaying, 163 strains of actinomycetes isolated from mangrove sediments were investigated for their potential to produce halogenated metabolites. The FADH2-dependent halogenase genes, identified in PCR-screening, were clustered in distinct clades in the phylogenetic analysis. The coexistence of either polyketide synthase (PKS) or nonribosomal peptide synthetase (NRPS) as the backbone synthetases in the strains harboring the halogenase indicated that these strains had the potential to produce structurally diversified antibiotics. As a validation, a new enduracidin producer, Streptomyces atrovirens MGR140, was identified and confirmed by gene disruption and HPLC analysis. Moreover, a putative ansamycin biosynthesis gene cluster was detected in Streptomyces albogriseolus MGR072. Our results highlight that combined genome mining is an efficient technique to tap promising sources of halogenated natural products synthesized by mangrove-derived actinomycetes.
Highlights
Mangroves, unique habitats in tropical and subtropical tidal areas, are known to be highly productive ecosystems [1]
To exploit the potential of halogenated natural products from mangrove-derived actinomycetes, we investigated the diversity of FADH2-dependent halogenases in 163 mangrove-derived actinomycetes and evaluated the potential of these strains to produce halogenated metabolites
The bioactivities of the strains harboring these halogenase genes were evaluated using anti-microorganism bioassays with five test strains and anti-tumor assays with three cell lines (Figure 1)
Summary
Unique habitats in tropical and subtropical tidal areas, are known to be highly productive ecosystems [1]. There is unambiguous evidence that the mangrove ecosystem contains a large diversity of actinomycetes, which have the potential of producing anti-infection and anti-tumor bioactive secondary metabolites [2,3,4]. Unique bioactive compounds have been obtained from mangrove-derived actinomycetes [4,5,6], how to tap the treasure trove of natural products produced by mangrove-derived actinomycetes is still of interest to drug developers. Intensive chemical exploitation of natural products always led to the identification of already known compounds [7,8]. These situations greatly hamper the discovery of novel secondary metabolites from microorganisms. Polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) are multi-domain enzymes or enzyme complexes that produce pharmaceutic important polyketides and nonribosomal peptides, respectively [11], but only targeting the conservative domains in either PKS or NRPS will always get more than one hit that belongs to different biosynthesis gene clusters
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