科研之友
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摘要
<jats:title>ABSTRACT</jats:title> <jats:p> Bacteria possess an amazing capacity to synthesize a diverse range of structurally complex, bioactive natural products known as specialized (or secondary) metabolites. Many of these specialized metabolites are used as clinical therapeutics, while others have important ecological roles in microbial communities. The biosynthetic gene clusters (BGCs) that generate these metabolites can be identified in bacterial genome sequences using their highly conserved genetic features. We analyzed an unprecedented 1,566 bacterial genomes from <jats:italic>Bacillus</jats:italic> species and identified nearly 20,000 BGCs. By comparing these BGCs to one another as well as a curated set of known specialized metabolite BGCs, we discovered that the majority of <jats:italic>Bacillus</jats:italic> natural products are comprised of a small set of highly conserved, well-distributed, known natural product compounds. Most of these metabolites have important roles influencing the physiology and development of <jats:italic>Bacillus</jats:italic> species. We identified, in addition to these characterized compounds, many unique, weakly conserved BGCs scattered across the genus that are predicted to encode unknown natural products. Many of these “singleton” BGCs appear to have been acquired via horizontal gene transfer. Based on this large-scale characterization of metabolite production in the <jats:italic>Bacilli</jats:italic> , we go on to connect the alkylpyrones, natural products that are highly conserved but previously biologically uncharacterized, to a role in <jats:italic>Bacillus</jats:italic> physiology: inhibiting spore development. </jats:p> <jats:p> <jats:bold>IMPORTANCE</jats:bold> <jats:italic>Bacilli</jats:italic> are capable of producing a diverse array of specialized metabolites, many of which have gained attention for their roles as signals that affect bacterial physiology and development. Up to this point, however, the <jats:italic>Bacillus</jats:italic> genus’s metabolic capacity has been underexplored. We undertook a deep genomic analysis of 1,566 <jats:italic>Bacillus</jats:italic> genomes to understand the full spectrum of metabolites that this bacterial group can make. We discovered that the majority of the specialized metabolites produced by <jats:italic>Bacillus</jats:italic> species are highly conserved, known compounds with important signaling roles in the physiology and development of this bacterium. Additionally, there is significant unique biosynthetic machinery distributed across the genus that might lead to new, unknown metabolites with diverse biological functions. Inspired by the findings of our genomic analysis, we speculate that the highly conserved alkylpyrones might have an important biological activity within this genus. We go on to validate this prediction by demonstrating that these natural products are developmental signals in <jats:italic>Bacillus</jats:italic> and act by inhibiting sporulation. </jats:p>
- 出版日期2017-12
