PDF(Pubmed)
Abstract：
Microbial NAT enzymes, which employ acyl-CoA to acylate aromatic amines and hydrazines, have been well-studied for their role in xenobiotic metabolism. Some homologues have also been linked to secondary metabolism, but this function of NAT enzymes is not as well-known. For this comparative study, we surveyed sequenced microbial genomes to update the list of formally annotated NAT genes, adding over 4000 new sequences (mainly bacterial, but also archaeal, fungal and protist) and portraying a broad but not universal distribution of NATs in the microbiocosmos. Localization of NAT sequences within microbial gene clusters was not a rare finding, and this association was evident across all main types of biosynthetic gene clusters (BGCs) implicated in secondary metabolism. Interrogation of the MIBiG database for experimentally characterized clusters with NAT genes further supports that secondary metabolism must be a major function for microbial NAT enzymes and should not be overlooked by researchers in the field. We also show that NAT sequences can be associated with bacterial plasmids potentially involved in horizontal gene transfer. Combined, our computational predictions and MIBiG literature findings reveal the extraordinary functional diversification of microbial NAT genes, prompting further research into their role in predicted BGCs with as yet uncharacterized function.
摘要：
微生物NAT酶，使用酰基辅酶A酰化芳族胺和肼，已经对它们在外源性生物代谢中的作用进行了充分的研究。一些同源物也与次级代谢有关，但是NAT酶的这种功能并不为人所知。对于这项比较研究，我们调查了测序的微生物基因组，以更新正式注释的NAT基因列表，添加4000多个新序列(主要是细菌，而且还有古细菌，真菌和原生生物），并描绘了微生物宇宙中NAT的广泛但非普遍分布。NAT序列在微生物基因簇中的定位并不是一个罕见的发现，并且这种关联在涉及次级代谢的所有主要类型的生物合成基因簇（BGC）中都很明显。对具有NAT基因的实验特征簇的MIBIG数据库的询问进一步支持次级代谢必须是微生物NAT酶的主要功能，并且不应该被该领域的研究人员忽视。我们还表明NAT序列可以与可能参与水平基因转移的细菌质粒相关联。合并,我们的计算预测和MIBIG文献发现揭示了微生物NAT基因的非凡功能多样化，促使进一步研究它们在预测的功能尚未表征的BGC中的作用。
