Data from: Phylum-wide comparative genomics unravel the diversity of secondary metabolism in Cyanobacteria

Background: Cyanobacteria are an ancient lineage of photosynthetic bacteria from which hundreds of natural products have been described, including many notorious toxins but also potent natural products of interest to the pharmaceutical and biotechnological industries. Many of these compounds are the products of non-ribosomal peptide synthetase (NRPS) or polyketide synthase (PKS) pathways. However, current understanding of the diversification of these pathways is largely based on the chemical structure of the bioactive compounds, while the evolutionary forces driving their remarkable chemical diversity are poorly understood. Results: We carried out a phylum-wide investigation of genetic diversification of the cyanobacterial NRPS and PKS pathways for the production of bioactive compounds. 452 NRPS and PKS gene clusters were identified from 89 cyanobacterial genomes, revealing a clear burst in late-branching lineages. Our genomic analysis further grouped the clusters into 286 highly diversified cluster families (CF) of pathways. Some CFs appeared vertically inherited, while others presented a more complex evolutionary history. Only a few horizontal gene transfers were evidenced amongst strongly conserved CFs in the phylum, while several others have undergone drastic gene shuffling events, which could result in the observed diversification of the pathways. Conclusions: Therefore, in addition to toxin production, several NRPS and PKS gene clusters are devoted to important cellular processes of these bacteria such as nitrogen fixation and iron uptake. The majority of the biosynthetic clusters identified here have unknown end products, highlighting the power of genome mining for the discovery of new natural products.背景：蓝细菌是一类古老的光合细菌演化支，目前已从中报道了数百种天然产物，其中既包括诸多臭名昭著的毒素，也包含医药与生物技术产业关注的强效天然产物。这类化合物大多由非核糖体肽合成酶（non-ribosomal peptide synthetase, NRPS）或聚酮合酶（polyketide synthase, PKS）通路合成。然而，当前对这些通路演化多样化的认知大多基于生物活性化合物的化学结构，而驱动其产生显著化学多样性的演化驱动力仍尚不明确。结果：本研究针对蓝细菌用于合成生物活性化合物的NRPS与PKS通路开展了门水平范围的遗传多样化分析。从89个蓝细菌基因组中共鉴定出452个NRPS和PKS基因簇，揭示出晚分化演化支中存在明显的基因簇爆发现象。进一步的基因组分析将这些基因簇划分为286个高度多样化的通路簇家族（cluster families, CF）。部分CF呈现垂直遗传特征，其余则展现出更为复杂的演化历史。在该门内高度保守的CF中仅发现少量水平基因转移事件，而其余多个CF则经历了剧烈的基因重排过程，这可能是导致上述通路多样化的原因。结论：因此，除了毒素合成之外，部分NRPS和PKS基因簇还参与了这类细菌的重要细胞过程，例如固氮作用与铁摄取。本研究鉴定的大多数生物合成基因簇的终产物仍未知，这凸显了基因组挖掘在发现新型天然产物方面的巨大潜力。