Abstract Ecological diversity in fungi is largely defined by metabolic traits, including the ability to produce secondary or “specialized” metabolites (SMs) that mediate interactions with other organisms. Fungal SM pathways are frequently encoded in biosynthetic gene clusters (BGCs), which facilitate the identification and characterization of metabolic pathways. Variation in BGC composition reflects the diversity of their SM products. Recent studies have documented surprising diversity of BGC repertoires among isolates of the same fungal species, yet little is known about how this population-level variation is inherited across macroevolutionary timescales. Here, we applied a novel linkage-based algorithm to reveal previously unexplored dimensions of diversity in BGC composition, distribution, and repertoire across 101 species of Dothideomycetes, which are considered the most phylogenetically diverse class of fungi and known to produce many SMs. We predicted both complementary and overlapping sets of clustered genes compared with existing methods and identified novel gene pairs that associate with known secondary metabolite genes. We found that variation among sets of BGCs in individual genomes is due to nonoverlapping BGC combinations and that several BGCs have biased ecological distributions, consistent with niche-specific selection. We observed that total BGC diversity scales linearly with increasing repertoire size, suggesting that secondary metabolites have little structural redundancy in individual fungi. We project that there is substantial unsampled BGC diversity across specific families of Dothideomycetes, which will provide a roadmap for future sampling efforts. Our approach and findings lend new insight into how BGC diversity is generated and maintained across an entire fungal taxonomic class.
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This content will become publicly available on December 1, 2024
Uncovering a miltiradiene biosynthetic gene cluster in the Lamiaceae reveals a dynamic evolutionary trajectory
Abstract The spatial organization of genes within plant genomes can drive evolution of specialized metabolic pathways. Terpenoids are important specialized metabolites in plants with diverse adaptive functions that enable environmental interactions. Here, we report the genome assemblies of Prunella vulgaris , Plectranthus barbatus , and Leonotis leonurus . We investigate the origin and subsequent evolution of a diterpenoid biosynthetic gene cluster (BGC) together with other seven species within the Lamiaceae (mint) family. Based on core genes found in the BGCs of all species examined across the Lamiaceae, we predict a simplified version of this cluster evolved in an early Lamiaceae ancestor. The current composition of the extant BGCs highlights the dynamic nature of its evolution. We elucidate the terpene backbones generated by the Callicarpa americana BGC enzymes, including miltiradiene and the terpene (+)-kaurene, and show oxidization activities of BGC cytochrome P450s. Our work reveals the fluid nature of BGC assembly and the importance of genome structure in contributing to the origin of metabolites.
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- NSF-PAR ID:
- 10420105
- Date Published:
- Journal Name:
- Nature Communications
- Volume:
- 14
- Issue:
- 1
- ISSN:
- 2041-1723
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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Streptomyces are 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 ofStreptomyces bacteria. We analysed draft genomes of 132Streptomyces isolates 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.Streptomyces isolates that colonize the same bat species or inhabit the same site exhibit greater overall genomic similarity than they do withStreptomyces from 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 theStreptomyces that carry them. Each genome carried between 19–65 BGCs (median=42.5) and varied even among members of the sameStreptomyces species. 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,Streptomyces genomes 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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Abstract Streptomyces bacteria are known for their prolific production of secondary metabolites, many of which have been widely used in human medicine, agriculture and animal health. To guide the effective prioritization of specific biosynthetic gene clusters (BGCs) for drug development and targeting the most prolific producer strains, knowledge about phylogenetic relationships ofStreptomyces species, genome-wide diversity and distribution patterns of BGCs is critical. We used genomic and phylogenetic methods to elucidate the diversity of major classes of BGCs in 1,110 publicly availableStreptomyces genomes. Genome mining ofStreptomyces reveals high diversity of BGCs and variable distribution patterns in theStreptomyces phylogeny, even among very closely related strains. The most common BGCs are non-ribosomal peptide synthetases, type 1 polyketide synthases, terpenes, and lantipeptides. We also found that numerousStreptomyces species harbor BGCs known to encode antitumor compounds. We observed that strains that are considered the same species can vary tremendously in the BGCs they carry, suggesting that strain-level genome sequencing can uncover high levels of BGC diversity and potentially useful derivatives of any one compound. These findings suggest that a strain-level strategy for exploring secondary metabolites for clinical use provides an alternative or complementary approach to discovering novel pharmaceutical compounds from microbes. -
null (Ed.)Abstract Background Antibiotic-producing Streptomyces bacteria are ubiquitous in nature, yet most studies of its diversity have focused on free-living strains inhabiting diverse soil environments and those in symbiotic relationship with invertebrates. Results We studied the draft genomes of 73 Streptomyces isolates sampled from the skin (wing and tail membranes) and fur surfaces of bats collected in Arizona and New Mexico. We uncovered large genomic variation and biosynthetic potential, even among closely related strains. The isolates, which were initially identified as three distinct species based on sequence variation in the 16S rRNA locus, could be distinguished as 41 different species based on genome-wide average nucleotide identity. Of the 32 biosynthetic gene cluster (BGC) classes detected, non-ribosomal peptide synthetases, siderophores, and terpenes were present in all genomes. On average, Streptomyces genomes carried 14 distinct classes of BGCs (range = 9–20). Results also revealed large inter- and intra-species variation in gene content (single nucleotide polymorphisms, accessory genes and singletons) and BGCs, further contributing to the overall genetic diversity present in bat-associated Streptomyces . Finally, we show that genome-wide recombination has partly contributed to the large genomic variation among strains of the same species. Conclusions Our study provides an initial genomic assessment of bat-associated Streptomyces that will be critical to prioritizing those strains with the greatest ability to produce novel antibiotics. It also highlights the need to recognize within-species variation as an important factor in genetic manipulation studies, diversity estimates and drug discovery efforts in Streptomyces .more » « less
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Davies, Julian E. (Ed.)ABSTRACT Bacteria isolated from soils are major sources of specialized metabolites, including antibiotics and other compounds with clinical value that likely shape interactions among microbial community members and impact biogeochemical cycles. Yet, isolated lineages represent a small fraction of all soil bacterial diversity. It remains unclear how the production of specialized metabolites varies across the phylogenetic diversity of bacterial species in soils and whether the genetic potential for production of these metabolites differs with soil depth and vegetation type within a geographic region. We sampled soils and saprolite from three sites in a northern California Critical Zone Observatory with various vegetation and bedrock characteristics and reconstructed 1,334 metagenome-assembled genomes containing diverse biosynthetic gene clusters (BGCs) for secondary metabolite production. We obtained genomes for prolific producers of secondary metabolites, including novel groups within the Actinobacteria , Chloroflexi , and candidate phylum “ Candidatus Dormibacteraeota.” Surprisingly, one genome of a candidate phyla radiation (CPR) bacterium coded for a ribosomally synthesized linear azole/azoline-containing peptide, a capacity we found in other publicly available CPR bacterial genomes. Overall, bacteria with higher biosynthetic potential were enriched in shallow soils and grassland soils, with patterns of abundance of BGC type varying by taxonomy. IMPORTANCE Microbes produce specialized compounds to compete or communicate with one another and their environment. Some of these compounds, such as antibiotics, are also useful in medicine and biotechnology. Historically, most antibiotics have come from soil bacteria which can be isolated and grown in the lab. Though the vast majority of soil bacteria cannot be isolated, we can extract their genetic information and search it for genes which produce these specialized compounds. These understudied soil bacteria offer a wealth of potential for the discovery of new and important microbial products. Here, we identified the ability to produce these specialized compounds in diverse and novel bacteria in a range of soil environments. This information will be useful to other researchers who wish to isolate certain products. Beyond their use to humans, understanding the distribution and function of microbial products is key to understanding microbial communities and their effects on biogeochemical cycles.more » « less
