Phylogenomic analysis of the diversity of graspetides and proteins involved in their biosynthesis.

Phylogenomic analysis of the diversity of graspetides and proteins involved in their biosynthesis.
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DOI:
10.1186/s13062-022-00320-2
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发表时间:
2022-03-21
期刊:
影响因子:
5.5
通讯作者:
Koonin EV
Koonin EV
中科院分区:
生物学2区
文献类型:
--
作者:
Makarova KS;Blackburne B;Wolf YI;Nikolskaya A;Karamycheva S;Espinoza M;Barry CE 3rd;Bewley CA;Koonin EV

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细菌和古细菌产生大量的修饰肽,这些肽参与各种形式的微生物间冲突或交流。大类这样的肽是核糖体合成的翻译后修饰肽(RIPP),并且主要的RIPP组是草肽,以催化这些肽中内酰胺和内酯键形成的ATP-草肽连接酶命名。蚱蜢的多样性,在各自的生物合成基因簇(BGC)中编码的多种蛋白质及其进化尚未得到充分详细的研究。在这项工作中,我们试图全面分析的graspetide编码的BGC和报告的各种新的graspetide组以及辅助蛋白质参与graspetide的生物合成和表达。我们编制了一个全面的,手动策划的一套graspetides,其中包括174个家庭,包括115个新的家庭与不同的模式的氨基酸涉及大环化和进一步修改,大约三倍的已知graspetide多样性。我们推导出的标志图案的前导区的graspetide前体,可用于促进graspetide预测。在以前不知道编码RIPPs的细菌部门中鉴定了草肽生物合成基因簇和特定前体,特别是候选门辐射的寄生和共生细菌。我们鉴定了拟杆菌特异性生物合成基因簇(BGC),其中包括在相同基因座中编码的具有显着多样性的蚱蜢,这些基因座预计会被相同的ATP-抓取连接酶修饰。我们详细研究了最近鉴定的黄绿菌素BGC的进化,表明重复和双链基因交换都有助于在进化过程中的蝗虫的多样化。我们证明了先前未被怀疑的多样性的graspetide序列,即使是那些与密切相关的ATP抓酶。发现了几个以前未被注意到的与草肽生物合成基因簇相关的蛋白质家族。这项工作的结果大大扩大了已知的RIPP的多样性,并可以利用进一步推进其识别方法。在线版本包含补充材料,可通过10.1186/s13062-022-00320-2获得。
Bacteria and archaea produce an enormous diversity of modified peptides that are involved in various forms of inter-microbial conflicts or communication. A vast class of such peptides are Ribosomally synthesized, Postranslationally modified Peptides (RiPPs), and a major group of RiPPs are graspetides, so named after ATP-grasp ligases that catalyze the formation of lactam and lactone linkages in these peptides. The diversity of graspetides, the multiple proteins encoded in the respective Biosynthetic Gene Clusters (BGCs) and their evolution have not been studied in full detail. In this work, we attempt a comprehensive analysis of the graspetide-encoding BGCs and report a variety of novel graspetide groups as well as ancillary proteins implicated in graspetide biosynthesis and expression. We compiled a comprehensive, manually curated set of graspetides that includes 174 families including 115 new families with distinct patterns of amino acids implicated in macrocyclization and further modification, roughly tripling the known graspetide diversity. We derived signature motifs for the leader regions of graspetide precursors that could be used to facilitate graspetide prediction. Graspetide biosynthetic gene clusters and specific precursors were identified in bacterial divisions not previously known to encode RiPPs, in particular, the parasitic and symbiotic bacteria of the Candidate phyla radiation. We identified Bacteroides-specific biosynthetic gene clusters (BGC) that include remarkable diversity of graspetides encoded in the same loci which predicted to be modified by the same ATP-grasp ligase. We studied in details evolution of recently characterized chryseoviridin BGCs and showed that duplication and horizonal gene exchange both contribute to the diversification of the graspetides during evolution. We demonstrate previously unsuspected diversity of graspetide sequences, even those associated with closely related ATP-grasp enzymes. Several previously unnoticed families of proteins associated with graspetide biosynthetic gene clusters are identified. The results of this work substantially expand the known diversity of RiPPs and can be harnessed to further advance approaches for their identification. The online version contains supplementary material available at 10.1186/s13062-022-00320-2.
DOI: 10.1073/pnas.1706849114
发表时间: 2017-11-07
影响因子: 11.1
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期刊: MOLECULAR AND GENERAL GENETICS
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