Zhang Anxin, Zhang Shu, Xu Xinran, Yin Wen-Bing
State Key Laboratory of Microbial Diversity and Innovative Utilization, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
Medical School, University of Chinese Academy of Sciences, Beijing 100049, China.
J Fungi (Basel). 2025 Jan 17;11(1):72. doi: 10.3390/jof11010072.
Fungal secondary metabolism (SM) is highly correlated with physiological processes that are typically regulated by pleiotropic regulators. In this study, we purposefully altered , a crucial regulator associated with oxidative stress in CGMCC 3.1066. After the knockout of , a novel polyketide (PK) raistrilide A () and the known nonribosomal peptide (NRP) tunicoidine () subsequently disappeared. Notably, compound is a rare octaketone derivative and contains two unsubstituted -double bonds, demonstrating its unique biosynthetic mechanism. The knockout of resulted in the disappearance of - and greatly increased the susceptibility of Δ mutant strain to oxidative stress, rendering it nearly impossible to survive in such environments. At present, the strain showed no phenotypic or oxidative stress sensitivity differences compared to the wild-type strain. Our findings highlight that the oxidative-stress-related transcription factor (TF) influences SM pathways in . . The manipulation of regulatory factors can guide the discovery of novel natural products (NPs).
真菌次级代谢（SM）与通常由多效性调节因子调控的生理过程高度相关。在本研究中，我们有目的地改变了CGMCC 3.1066中与氧化应激相关的关键调节因子。敲除该调节因子后，一种新型聚酮化合物（PK）雷斯特里利德A（）和已知的非核糖体肽（NRP）衣霉素（）随后消失。值得注意的是，化合物是一种罕见的八酮衍生物，含有两个未取代的 - 双键，表明其独特的生物合成机制。敲除导致 - 的消失，并大大增加了Δ突变菌株对氧化应激的敏感性，使其在这种环境中几乎无法存活。目前，该菌株与野生型菌株相比未表现出表型或氧化应激敏感性差异。我们的研究结果突出表明，与氧化应激相关的转录因子（TF）影响中的SM途径。调节因子的操纵可以指导新型天然产物（NPs）的发现。
