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苯乙酸（PAA）分解代谢途径分支点基因和 PAA 分解代谢基因簇外的基因协同参与 HYS 中铁载体 7-羟基色酮的生物合成。

The Gene of the Phenylacetic Acid (PAA) Catabolic Pathway Branching Point and outside the PAA Catabolon Gene Cluster Are Synergistically Involved in the Biosynthesis of the Iron Scavenger 7-Hydroxytropolone in HYS.

机构信息

Hubei Key Laboratory of Cell Homeostasis, College of Life Sciences, Wuhan University, Wuhan 430072, China.

出版信息

Int J Mol Sci. 2023 Aug 10;24(16):12632. doi: 10.3390/ijms241612632.

DOI:10.3390/ijms241612632
PMID:37628812
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10454607/
Abstract

The newly discovered iron scavenger 7-hydroxytropolone (7-HT) is secreted by HYS. In addition to possessing an iron-chelating ability, 7-HT has various other biological activities. However, 7-HT's biosynthetic pathway remains unclear. This study was the first to report that the phenylacetic acid (PAA) catabolon genes in cluster 2 are involved in the biosynthesis of 7-HT and that two genes, () and , are synergistically involved in the biosynthesis of 7-HT in HYS. Firstly, gene knockout and a sole carbon experiment indicated that the genes () and () were involved in the biosynthesis of 7-HT and participated in the PAA catabolon pathway in HYS; these genes were arranged in gene cluster 2 in HYS. Interestingly, ORF13 was a homologous protein of PaaZ, but () was not essential for the biosynthesis of 7-HT in HYS. A genome-wide BLASTP search, including gene knockout, complemented assays, and site mutation, showed that the gene homologous to the ECH domain of () is essential for the biosynthesis of 7-HT. Three key conserved residues of (Asp39, His44, and Gly62) were identified in HYS. Furthermore, () could not complement the role of in the production of 7-HT, and the single carbon experiment indicated that mainly participates in PAA catabolism. Overall, this study reveals a natural association between PAA catabolon and the biosynthesis of 7-HT in HYS. These two genes have a synergistic effect and different functions: is mainly involved in the degradation of PAA, while is mainly related to the biosynthesis of 7-HT in HYS. These findings complement our understanding of the mechanism of the biosynthesis of 7-HT in the genus .

摘要

新发现的铁螯合剂 7-羟基色酮（7-HT）由 HYS 分泌。除了具有螯合铁的能力外，7-HT 还具有多种其他生物活性。然而，7-HT 的生物合成途径尚不清楚。本研究首次报道了簇 2 中的苯乙酸（PAA）分解代谢基因参与 7-HT 的生物合成，并且两个基因（()和）协同参与 HYS 中 7-HT 的生物合成。首先，基因敲除和单碳实验表明，基因（()和）参与 7-HT 的生物合成，并参与 HYS 中的 PAA 分解代谢途径；这些基因在 HYS 中排列在基因簇 2 中。有趣的是，ORF13 是 PaaZ 的同源蛋白，但在 HYS 中，（）对于 7-HT 的生物合成不是必需的。全基因组 BLASTP 搜索，包括基因敲除、互补测定和位点突变，表明与（）的 ECH 结构域同源的基因对于 7-HT 的生物合成是必需的。在 HYS 中鉴定出（）的三个关键保守残基（Asp39、His44 和 Gly62）。此外，（）不能补充（）在 7-HT 产生中的作用，并且单碳实验表明（）主要参与 PAA 分解代谢。总的来说，本研究揭示了 PAA 分解代谢物与 HYS 中 7-HT 生物合成之间的天然关联。这两个基因具有协同作用和不同的功能：（）主要参与 PAA 的降解，而（）主要与 HYS 中 7-HT 的生物合成有关。这些发现补充了我们对属中 7-HT 生物合成机制的理解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0ec/10454607/93e102c3483d/ijms-24-12632-g008.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d0ec/10454607/93e102c3483d/ijms-24-12632-g008.jpg

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