Discovery of the Pseudomonas Polyyne Protegencin by a Phylogeny-Guided Study of Polyyne Biosynthetic Gene Cluster Diversity.
Discovery of the Pseudomonas Polyyne Protegencin by a Phylogeny-Guided Study of Polyyne Biosynthetic Gene Cluster Diversity.
复制标题
DOI：
10.1128/mbio.00715-21
复制
发表时间：
2021-08-31
期刊：
影响因子：
6.4
通讯作者：
Mahenthiralingam E
中科院分区：
文献类型：
--
作者：
Mullins AJ;Webster G;Kim HJ;Zhao J;Petrova YD;Ramming CE;Jenner M;Murray JAH;Connor TR;Hertweck C;Challis GL;Mahenthiralingam E
具有炔烃或多炔基团的天然产物已经从各种生物来源中分离出来，并具有广泛的生物活性。在细菌中，多炔类化合物的基本生物合成是已知的，但其生物合成基因簇(BGC)的分布及其与炔类生物合成的进化关系尚未得到解决。通过综合基因组和系统发育分析，探索了炔烃生物合成基因盒在细菌中的分布，揭示了多次水平基因转移事件的证据。在研究了炔烃和多炔生物合成之间的进化关系后，发现了一个单系分支，该分支含有一个保守的七个多炔生物合成基因盒，而这个保守的三基因合成盒是在此基础上建立起来的。对保守的多炔基因盒的进一步多样性图谱显示，在几个假单胞菌种中存在一个未鉴定的多炔BGC的系统发育亚支，命名为PGN。途径诱变和高分辨分析化学表明，假单胞菌蛋白原PGN BGC指导了一种新的多炔的生物合成，即蛋白粘附素。通过BGC诱变和分析化学对聚炔产生背后的生物合成逻辑的探索，强调了三种去饱和酶蛋白和硫代酯酶在P.progengenpgn和Trinickia caryophylli(以前称为Burkholderia caryophylli)caryynencin途径中的重要性。我们统一和扩展了关于聚炔多样性的知识，并独特地证明了炔烃和聚炔生物合成基因簇在进化上是相关的，并在细菌中广泛分布。在现有的细菌基因组多样性上对保守的生物合成基因进行系统的定位被证明是发现新的天然产物和更好地了解聚炔生物合成的一种卓有成效的方法。
Natural products that possess alkyne or polyyne moieties have been isolated from a variety of biological sources and possess a broad a range of bioactivities. In bacteria, the basic biosynthesis of polyynes is known, but their biosynthetic gene cluster (BGC) distribution and evolutionary relationship to alkyne biosynthesis have not been addressed. Through comprehensive genomic and phylogenetic analyses, the distribution of alkyne biosynthesis gene cassettes throughout bacteria was explored, revealing evidence of multiple horizontal gene transfer events. After investigation of the evolutionary connection between alkyne and polyyne biosynthesis, a monophyletic clade was identified that possessed a conserved seven-gene cassette for polyyne biosynthesis that built upon the conserved three-gene cassette for alkyne biosynthesis. Further diversity mapping of the conserved polyyne gene cassette revealed a phylogenetic subclade for an uncharacterized polyyne BGC present in several Pseudomonas species, designated pgn. Pathway mutagenesis and high-resolution analytical chemistry showed the Pseudomonas protegens pgn BGC directed the biosynthesis of a novel polyyne, protegencin. Exploration of the biosynthetic logic behind polyyne production, through BGC mutagenesis and analytical chemistry, highlighted the essentiality of a triad of desaturase proteins and a thioesterase in both the P. protegens pgn and Trinickia caryophylli (formerly Burkholderia caryophylli) caryoynencin pathways. We have unified and expanded knowledge of polyyne diversity and uniquely demonstrated that alkyne and polyyne biosynthetic gene clusters are evolutionarily related and widely distributed within bacteria. The systematic mapping of conserved biosynthetic genes across the available bacterial genomic diversity proved to be a fruitful method for discovering new natural products and better understanding polyyne biosynthesis.