Ma Man-Jing, Yu Wen-Chao, Sun Huai-Ying, Dong Bing-Cheng, Hu Gang-Ao, Zhou Zhen-Yi, Hua Yi, Basnet Buddha Bahadur, Yu Yan-Lei, Wang Hong, Wei Bin
College of Pharmaceutical Science & Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang Key Laboratory of Green, Low-Carbon, and Efficient Development of Marine Fishery Resources, Zhejiang University of Technology, Hangzhou 310014, China.
Central Department of Biotechnology, Tribhuvan University, Kathmandu, Nepal.
Synth Syst Biotechnol. 2024 Mar 21;9(3):381-390. doi: 10.1016/j.synbio.2024.03.015. eCollection 2024 Sep.
Rare actinomycete genera are highly recognized as a promising source of structurally diverse and bioactive natural products. Among these genera, and are two phylogenetically closely related and have been reported to encode some valuable biosynthetic enzymes and secondary metabolites. However, there is currently no relevant systematic research available to outline the linkage of genomic and metabolomics for specific secondary metabolites in these two promising genera. In this study, we first investigated the genus-specific secondary metabolic potential in and by comparing the diversity and novelty of their secondary metabolite biosynthetic gene clusters (BGCs). The specific secondary metabolites produced by two representative strains of these genera were comprehensively investigated using untargeted metabolomics techniques. The findings unveiled that the majority (95.4%) of the gene cluster families (GCFs) encoded by and were genus-specific, including NRPS GCFs encoding siderophores. The untargeted metabolomics analysis revealed that the metabolic profiles of two representative strains exhibit extensive specificity, with the culture medium having a big impact on the metabolic profiles. Besides, an MS-cluster featuring a series of hydroxamate-type siderophores was identified from JCM 9917, with two of them, including a novel one (N-deoxy arthrobactin A), being experimentally validated. The present study offers valuable insights for the targeted discovery of genus-specific natural products from microorganisms.
稀有放线菌属被高度认为是结构多样且具有生物活性的天然产物的一个有前景的来源。在这些属中，[具体属名1]和[具体属名2]在系统发育上密切相关，并且据报道编码一些有价值的生物合成酶和次生代谢产物。然而，目前尚无相关的系统研究来概述这两个有前景的属中特定次生代谢产物的基因组学和代谢组学之间的联系。在本研究中，我们首先通过比较它们次生代谢产物生物合成基因簇（BGCs）的多样性和新颖性，研究了[具体属名1]和[具体属名2]中属特异性的次生代谢潜力。使用非靶向代谢组学技术全面研究了这些属的两个代表性菌株产生的特定次生代谢产物。研究结果表明，[具体属名1]和[具体属名2]编码的基因簇家族（GCFs）中大多数（95.4%）是属特异性的，包括编码铁载体的NRPS GCFs。非靶向代谢组学分析表明，两个代表性菌株的代谢谱表现出广泛的特异性，培养基对代谢谱有很大影响。此外，从[具体属名1] JCM 9917中鉴定出一个以一系列异羟肟酸型铁载体为特征的MS簇，其中两个，包括一个新的（N-脱氧节杆菌素A），经过实验验证。本研究为从微生物中靶向发现属特异性天然产物提供了有价值的见解。
