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Streptomycesare prolific producers of secondary metabolites from which many clinically useful compounds have been derived. They inhabit diverse habitats but have rarely been reported in vertebrates. Here, we aim to determine to what extent the ecological source (bat host species and cave sites) influence the genomic and biosynthetic diversity ofStreptomycesbacteria. We analysed draft genomes of 132Streptomycesisolates sampled from 11 species of insectivorous bats from six cave sites in Arizona and New Mexico, USA. We delineated 55 species based on the genome-wide average nucleotide identity and core genome phylogenetic tree.Streptomycesisolates that colonize the same bat species or inhabit the same site exhibit greater overall genomic similarity than they do withStreptomycesfrom other bat species or sites. However, when considering biosynthetic gene clusters (BGCs) alone, BGC distribution is not structured by the ecological or geographical source of theStreptomycesthat carry them. Each genome carried between 19–65 BGCs (median=42.5) and varied even among members of the sameStreptomycesspecies. Nine major classes of BGCs were detected in ten of the 11 bat species and in all sites: terpene, non-ribosomal peptide synthetase, polyketide synthase, siderophore, RiPP-like, butyrolactone, lanthipeptide, ectoine, melanin. Finally,Streptomycesgenomes carry multiple hybrid BGCs consisting of signature domains from two to seven distinct BGC classes. Taken together, our results bring critical insights to understandingStreptomyces-bat ecology and BGC diversity that may contribute to bat health and in augmenting current efforts in natural product discovery, especially from underexplored or overlooked environments.
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Discovery and Biosynthesis of a Structurally Dynamic Antibacterial Diterpenoid
Abstract A new bicyclic diterpenoid, benditerpenoic acid, was isolated from soil‐dwellingStreptomycessp. (CL12‐4). We sequenced the bacterial genome, identified the responsible biosynthetic gene cluster, verified the function of the terpene synthase, and heterologously produced the core diterpene. Comparative bioinformatics indicated thisStreptomycesstrain is phylogenetically unique and possesses nine terpene synthases. The absolute configurations of the newtrans‐fused bicyclo[8.4.0]tetradecanes were achieved by extensive spectroscopic analyses, including Mosher's analysis,J‐based coupling analysis, and computations based on sparse NMR‐derived experimental restraints. Interestingly, benditerpenoic acid exists in two distinct ring‐flipped bicyclic conformations with a rotational barrier of ≈16 kcal mol−1in solution. The diterpenes exhibit moderate antibacterial activity against Gram‐positive bacteria including methicillin and multi‐drug resistantStaphylococcus aureus. This is a rare example of an eunicellane‐type diterpenoid from bacteria and the first identification of a diterpene synthase and biosynthetic gene cluster responsible for the construction of the eunicellane scaffold.
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- Award ID(s):
- 1808717
- PAR ID:
- 10228337
- Publisher / Repository:
- Wiley Blackwell (John Wiley & Sons)
- Date Published:
- Journal Name:
- Angewandte Chemie International Edition
- Volume:
- 60
- Issue:
- 25
- ISSN:
- 1433-7851
- Page Range / eLocation ID:
- p. 14163-14170
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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