Chen Shanchong, Zhang Chi, Zhang Lihan
Department of Chemistry, Zhejiang University, Hangzhou, 310027, Zhejiang Province, China.
Key Laboratory of Precise Synthesis of Functional Molecules of Zhejiang Province, School of Science, Westlake University, 18 Shilongshan Road, Hangzhou, 310024, Zhejiang Province, China.
Angew Chem Int Ed Engl. 2022 Jun 13;61(24):e202202286. doi: 10.1002/anie.202202286. Epub 2022 Apr 21.
Aromatic polyketides biosynthesized by microorganisms are a prominent class of natural products widely used in clinical treatments. Although genome mining approaches have accelerated the discovery of these molecules, the molecular diversity, abundance, and distribution of bacterial aromatic polyketides at a global scale remain elusive. Here, we provide a global atlas of bacterial aromatic polyketides based on large-scale analysis of type II polyketide synthases. We first established the chain length factor protein as a marker that can predict both chemical class and molecular uniqueness of the biosynthetic product, and analyzed the abundance, taxonomic distribution, estimated structural diversity, and the total number of aromatic polyketides in bacteria. We further show the identification of oryzanaphthopyrans with an unprecedented angular naphthopyran scaffold from a rare actinobacterium by genome mining guided by the global atlas. These results serve as a compass for exploiting the entire type II polyketide synthase-derived aromatic polyketides in bacteria.
微生物生物合成的芳香族聚酮化合物是一类重要的天然产物，广泛应用于临床治疗。尽管基因组挖掘方法加速了这些分子的发现，但全球范围内细菌芳香族聚酮化合物的分子多样性、丰度和分布情况仍不清楚。在此，我们基于对II型聚酮合酶的大规模分析，提供了一份细菌芳香族聚酮化合物的全球图谱。我们首先将链长因子蛋白确立为一种标志物，它可以预测生物合成产物的化学类别和分子独特性，并分析了细菌中芳香族聚酮化合物的丰度、分类分布、估计的结构多样性以及总数。我们进一步展示了通过全球图谱指导的基因组挖掘，从一种罕见的放线菌中鉴定出具有前所未有的角萘并吡喃骨架的稻瘟萘并吡喃。这些结果为开发细菌中整个II型聚酮合酶衍生的芳香族聚酮化合物提供了指导。
