Constructing a Myxobacterial Natural Product Database to Facilitate NMR-Based Metabolomics Bioprospecting of Myxobacteria,Analytical Chemistry

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Constructing a Myxobacterial Natural Product Database to Facilitate NMR-Based Metabolomics Bioprospecting of Myxobacteria
Analytical Chemistry ( IF 6.7 ) Pub Date : 2023-03-14 , DOI: 10.1021/acs.analchem.2c05145
De-Gao Wang ₁ , Chao-Yi Wang ₁ , Jia-Qi Hu ₁ , Jing-Jing Wang ₁ , Wen-Chao Liu ₁ , Wen-Juan Zhang ₁ , Xin-Ran Du ₁ , Han Wang ₁ , Le-Le Zhu ₁ , Hai-Yan Sui ₁ , Yue-Zhong Li ₁ , Changsheng Wu ₁

Affiliation

Myxobacteria are fascinating prokaryotes featuring a potent capacity for producing a wealth of bioactive molecules with intricate chemical topology as well as intriguing enzymology, and thus it is critical to developing an efficient pipeline for bioprospecting. Herein, we construct the database MyxoDB, the first public compendium solely dedicated to myxobacteria, which enabled us to provide an overview of the structural diversity and taxonomic distribution of known myxobacterial natural products. Moreover, we demonstrated that the cutting-edge NMR-based metabolomics was effective to differentiate the biosynthetic priority of myxobacteria, whereby MyxoDB could greatly streamline the dereplication of multifarious known compounds and accordingly speed up the discovery of new compounds. This led to the rapid identification of a class of linear di-lipopeptides (archangimins) and a rare rearranged sterol (corasterol) that were endowed with unique chemical architectures and/or biosynthetic enzymology. We also showcased that NMR-based metabolomics, MyxoDB, and genomics can also work concertedly to accelerate the targeted discovery of a polyketidic compound pyxipyrrolone C. All in all, this study sets the stage for the discovery of many more novel natural products from underexplored myxobacterial resources.

中文翻译：

构建粘细菌天然产物数据库以促进基于 NMR 的粘细菌代谢组学生物勘探

粘细菌是令人着迷的原核生物，具有产生大量具有复杂化学拓扑结构和有趣酶学的生物活性分子的强大能力，因此它对于开发有效的生物勘探管道至关重要。在此，我们构建了数据库 MyxoDB，这是第一个专门用于粘细菌的公共纲要，它使我们能够概述已知粘细菌天然产物的结构多样性和分类分布。此外，我们证明了基于核磁共振的前沿代谢组学可有效区分粘细菌的生物合成优先级，由此 MyxoDB 可以极大地简化多种已知化合物的脱复制，从而加快新化合物的发现。这导致快速鉴定了一类线性二脂肽 (archangimins) 和一种罕见的重排甾醇 (corasterol)，它们具有独特的化学结构和/或生物合成酶学。我们还展示了基于 NMR 的代谢组学、MyxoDB 和基因组学也可以协同工作，以加速聚酮化合物吡咯酮 C 的靶向发现。总而言之，这项研究为从未充分开发的粘细菌中发现更多新型天然产物奠定了基础资源。

更新日期：2023-03-14

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