Genome Mining and Heterologous Expression Reveal Two Distinct Families of Lasso Peptides Highly Conserved in Endofungal Bacteria.,ACS Chemical Biology

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Genome Mining and Heterologous Expression Reveal Two Distinct Families of Lasso Peptides Highly Conserved in Endofungal Bacteria.
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2019-12-18 , DOI: 10.1021/acschembio.9b00805
Evgeni V Bratovanov ₁ , Keishi Ishida ₁ , Beatrix Heinze ₁ , Sacha J Pidot ₂ , Timothy P Stinear ₂ , Julian D Hegemann _{3,

4} , Mohamed A Marahiel ₄ , Christian Hertweck _{1,

5}

Affiliation

Genome mining identified the fungal-bacterial endosymbiosis Rhizopus microsporus-Mycetohabitans (previously Burkholderia) rhizoxinica as a rich source of novel natural products. However, most of the predicted compounds have remained cryptic. In this study, we employed heterologous expression to isolate and characterize three ribosomally synthesized and post-translationally modified peptides with lariat topology (lasso peptides) from the endosymbiont M. rhizoxinica: burhizin-23, mycetohabin-16, and mycetohabin-15. Through coexpression experiments, it was shown that an orphan gene product results in mature mycetohabin-15, albeit encoded remotely from the core biosynthetic gene cluster. Comparative genomics revealed that mycetohabins are highly conserved among M. rhizoxinica and related endosymbiotic bacteria. Gene knockout and reinfection experiments indicated that the lasso peptides are not crucial for establishing symbiosis; instead, the peptides are exported into the environment during endosymbiosis. This is the first report on lasso peptides from endosymbiotic bacteria.

中文翻译：

基因组挖掘和异源表达揭示了在真菌内细菌中高度保守的套索肽的两个不同家族。

基因组采矿确定了真菌-细菌共生微孢根霉-真菌菌根霉（原伯克霍尔德氏菌）根瘤菌是丰富的新型天然产物。但是，大多数预测的化合物仍是隐秘的。在这项研究中，我们采用异源表达来分离和鉴定来自内生共生根瘤菌的三种具有核糖体合成和翻译后修饰的肽（套索肽）：burhizin-23，mycetohabin-16和mycetohabin-15。通过共表达实验，表明孤儿基因产物可导致成熟的霉菌毒素15，尽管其编码远离核心生物合成基因簇。比较基因组学表明，霉菌毒素在根瘤菌和相关内共生细菌中高度保守。基因敲除和再感染实验表明，套索肽对于建立共生不是关键。而是在共生过程中将肽输出到环境中。这是关于来自内共生细菌的套索肽的首次报道。

更新日期：2019-12-04

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