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 Chemistry and Biochemistry, University of California, Santa Cruz, Santa Cruz, CA 95064, USA.
Cell. 2014 Sep 11;158(6):1402-1414. doi: 10.1016/j.cell.2014.08.032.
In complex biological systems, small molecules often mediate microbe-microbe and microbe-host interactions. Using a systematic approach, we identified 3,118 small-molecule biosynthetic gene clusters (BGCs) in genomes of human-associated bacteria and studied their representation in 752 metagenomic samples from the NIH Human Microbiome Project. Remarkably, we discovered that BGCs for a class of antibiotics in clinical trials, thiopeptides, are widely distributed in genomes and metagenomes of the human microbiota. We purified and solved the structure of a thiopeptide antibiotic, lactocillin, from a prominent member of the vaginal microbiota. We demonstrate that lactocillin has potent antibacterial activity against a range of Gram-positive vaginal pathogens, and we show that lactocillin and other thiopeptide BGCs are expressed in vivo by analyzing human metatranscriptomic sequencing data. Our findings illustrate the widespread distribution of small-molecule-encoding BGCs in the human microbiome, and they demonstrate the bacterial production of drug-like molecules in humans. PAPERCLIP:
在复杂的生物系统中，小分子通常介导微生物-微生物和微生物-宿主的相互作用。我们采用系统的方法，在与人类相关的细菌基因组中鉴定出 3118 个小分子生物合成基因簇（BGC），并研究了它们在 NIH 人类微生物组计划的 752 个宏基因组样本中的代表性。值得注意的是，我们发现了一类正在临床试验中的抗生素，硫肽类抗生素，在人类微生物组的基因组和宏基因组中广泛分布。我们从阴道微生物组中的一个突出成员中分离并解析了一种硫肽抗生素 lactocillin 的结构。我们证明了 lactocillin 对一系列革兰氏阳性阴道病原体具有强大的抗菌活性，并且我们通过分析人类宏转录组测序数据表明 lactocillin 和其他硫肽 BGC 在体内表达。我们的研究结果说明了小分子编码 BGC 在人类微生物组中的广泛分布，并展示了细菌在人体内产生类似药物的分子。PAPERCLIP：
