Unveiling of Swainsonine Biosynthesis via a Multibranched Pathway in Fungi.,ACS Chemical Biology

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Unveiling of Swainsonine Biosynthesis via a Multibranched Pathway in Fungi.
ACS Chemical Biology ( IF 3.5 ) Pub Date : 2020-08-07 , DOI: 10.1021/acschembio.0c00466
Feifei Luo _{1,

2} , Song Hong ₂ , Bo Chen ₂ , Ying Yin ₂ , Guirong Tang ₂ , Fenglin Hu ₃ , Huizhan Zhang ₁ , Chengshu Wang _{2,

4}

Affiliation

The indolizidine alkaloid swainsonine (SW) is a deadly mycotoxin to livestock that can be produced by different plant-associated fungi, including the endophytic entomopathogenic fungi Metarhizium species. The SW biosynthetic gene cluster has been identified but the genetic mechanism of SW biosynthesis remains obscure. To unveil the SW biosynthetic pathway, we performed gene deletions in M. robertsii, heterologous expression of a core biosynthetic gene, substrate feedings, mass spectrometry, and bioassay analyses in this study. It was unveiled that SW is produced via a multibranched pathway by the hybrid nonribosomal peptide–polyketide synthase (NRPS-PKS) gene cluster in M. robertsii. The precursor pipecolic acid can be converted from lysine by both the SW biosynthetic cluster and the unclustered genes such as lysine cyclodeaminase. The hybrid NRPS-PKS enzyme produces three intermediates with and without domain skipping. Intriguingly, the biosynthetic process is coupled with the cis to trans nonenzymatic epimerization of C1-OH for both hydroxyl- and dihydroxyl-indolizidine intermediates. We also found that SW production was dispensable for fungal colonization of plants and infection of insect hosts. Functional characterization of the SW biosynthetic genes in this study may benefit the safe use of Metarhizium fungi as insect biocontrol agents and the management of livestock pastures from SW contamination by genetic manipulation of the toxin-producing fungi.

中文翻译：

通过真菌中的多分支途径揭示Swainsonine生物合成。

吲哚并立生物碱swainsonine（SW）是家畜的致命霉菌毒素，可由不同的植物相关真菌（包括内生昆虫病原真菌Metrahizium种）产生。SW生物合成基因簇已被确定，但SW生物合成的遗传机制仍然不清楚。为了揭示SW生物合成途径，我们在本研究中进行了罗氏沼虾的基因删除，核心生物合成基因的异源表达，底物进料，质谱和生物测定分析。有人推出该SW由混合动力非核糖体肽-聚酮化合物合酶（NRPS-PKS）在基因簇通过一个多分支途径产生M. robertsii。SW生物合成簇和未聚簇的基因（例如赖氨酸环脱氨酶）都可以从赖氨酸转化前体哌酸。杂化NRPS-PKS酶可产生带和不带域跳跃的三种中间体。有趣的是，生物合成过程加上顺向反式C1-OH的非酶差向异构化两个羟基和二羟基吲哚里中间体。我们还发现，SW的产生对于植物的真菌定植和昆虫宿主的感染是必不可少的。西南合成基因在这项研究中的功能特性可能受益的安全使用绿僵菌 作为昆虫生物防治剂的真菌，以及通过对产毒真菌的基因操作对SW污染的牲畜牧场进行管理。

更新日期：2020-09-20

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