Department of Bioengineering and Therapeutic Sciences and the California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, CA 94158, USA.
Department of Microbial Physiology, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 7, 9747AG Groningen, The Netherlands; Groningen Bioinformatics Centre, Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, Nijenborgh 7, 9747AG Groningen, The Netherlands.
Cell. 2014 Jul 17;158(2):412-421. doi: 10.1016/j.cell.2014.06.034.
Although biosynthetic gene clusters (BGCs) have been discovered for hundreds of bacterial metabolites, our knowledge of their diversity remains limited. Here, we used a novel algorithm to systematically identify BGCs in the extensive extant microbial sequencing data. Network analysis of the predicted BGCs revealed large gene cluster families, the vast majority uncharacterized. We experimentally characterized the most prominent family, consisting of two subfamilies of hundreds of BGCs distributed throughout the Proteobacteria; their products are aryl polyenes, lipids with an aryl head group conjugated to a polyene tail. We identified a distant relationship to a third subfamily of aryl polyene BGCs, and together the three subfamilies represent the largest known family of biosynthetic gene clusters, with more than 1,000 members. Although these clusters are widely divergent in sequence, their small molecule products are remarkably conserved, indicating for the first time the important roles these compounds play in Gram-negative cell biology.
尽管已经发现了数百种细菌代谢产物的生物合成基因簇 (BGCs)，但我们对它们的多样性的了解仍然有限。在这里，我们使用一种新的算法系统地鉴定了广泛存在的微生物测序数据中的 BGCs。预测 BGCs 的网络分析揭示了大型基因簇家族，其中绝大多数尚未被描述。我们通过实验对最突出的家族进行了表征，该家族由分布在变形菌门中的数百个 BGC 的两个亚家族组成；它们的产物是芳基聚烯，一种带有芳基头部基团和聚烯尾部的脂质。我们鉴定出与第三个芳基聚烯 BGC 亚家族的遥远关系，这三个亚家族共同代表了已知最大的生物合成基因簇家族，拥有超过 1000 个成员。尽管这些簇在序列上有很大的差异，但它们的小分子产物却非常保守，这表明这些化合物在革兰氏阴性细胞生物学中起着重要作用。
