A phylogenetic and evolutionary analysis of antimycin biosynthesis.
A phylogenetic and evolutionary analysis of antimycin biosynthesis.
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DOI：
10.1099/mic.0.000572
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Seipke RF
中科院分区：
文献类型：
--
作者：
Joynt R;Seipke RF
链霉菌属和其他放线菌普遍存在于世界各地的不同环境中，是大多数抗生素的来源或灵感来源。基因组时代增强了对这些有价值的化学实体的生物合成的理解，并且还提供了一个了解天然产物生物合成基因簇的多样性和分布的窗口。抗霉素是线粒体细胞色素c还原酶的抑制剂，并且最近显示出抑制通常由癌细胞过度产生的Bcl-2/Bcl-XL相关的抗凋亡蛋白。在这里，我们确定了73个推定的抗霉素生物合成基因簇（BGC）在公开的放线菌基因组序列和分类的基础上存在或不存在的集群定位基因antP和antQ，编码犬尿氨酸酶和磷酸泛酰巯基乙胺转移酶（PPTase），分别。大多数BGC要么同时具有antP和antQ（L型），要么两者都不具有（S型），而少数BGC缺乏antP或antQ（分别为IQ型或IP型）。我们还评估了抗霉素生产者和BGC的地理分布和系统发育关系。我们发现，抗霉素BGC发生在五个七大洲，并经常从植物和其他高等生物体中分离。我们还提供了证据，两个不同的系统发育分支的抗霉素生产商和基因簇，从L-和I-型BGC描绘S-型。最后，我们的研究结果表明，祖先的抗霉素生产者窝藏的L型基因簇，主要是通过垂直传播传播，随后多样化成S-，IQ-和IP-形式的生物合成途径。
Streptomyces species and other Actinobacteria are ubiquitous in diverse environments worldwide and are the source of, or inspiration for, the majority of antibiotics. The genomic era has enhanced biosynthetic understanding of these valuable chemical entities and has also provided a window into the diversity and distribution of natural product biosynthetic gene clusters. Antimycin is an inhibitor of mitochondrial cytochrome c reductase and more recently was shown to inhibit Bcl-2/Bcl-XL-related anti-apoptotic proteins commonly overproduced by cancerous cells. Here we identify 73 putative antimycin biosynthetic gene clusters (BGCs) in publicly available genome sequences of Actinobacteria and classify them based on the presence or absence of cluster-situated genes antP and antQ, which encode a kynureninase and a phosphopantetheinyl transferase (PPTase), respectively. The majority of BGCs possess either both antP and antQ (L-form) or neither (S-form), while a minority of them lack either antP or antQ (IQ- or IP-form, respectively). We also evaluate the biogeographical distribution and phylogenetic relationships of antimycin producers and BGCs. We show that antimycin BGCs occur on five of the seven continents and are frequently isolated from plants and other higher organisms. We also provide evidence for two distinct phylogenetic clades of antimycin producers and gene clusters, which delineate S-form from L- and I-form BGCs. Finally, our findings suggest that the ancestral antimycin producer harboured an L-form gene cluster which was primarily propagated by vertical transmission and subsequently diversified into S-, IQ- and IP-form biosynthetic pathways.
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