Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, Los Angeles, CA 90089, USA.
Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, School of Pharmacy, 1985 Zonal Avenue, Los Angeles, CA 90089, USA; Graduate Institute of Pharmaceutical Science, Chia Nan University of Pharmacy and Science, Tainan 71710, Taiwan.
Fungal Genet Biol. 2022 May;160:103694. doi: 10.1016/j.fgb.2022.103694. Epub 2022 Apr 6.
Filamentous fungal secondary metabolites are an important source of bioactive components. Genome sequencing ofAspergillus terreusrevealed many silent secondary metabolite biosynthetic gene clusters presumed to be involved in producing secondary metabolites. Activation of silent gene clusters through overexpressing a pathway-specific regulator is an effective avenue for discovering novel fungal secondary metabolites. Replacement of the native promoter of the pathway-specific activator with the inducible Tet-on system to activate thetazpathway led to the discovery of a series of azaphilone secondary metabolites, among which azaterrilone A (1) was purified and identified for the first time. Genetic deletion of core PKS genes and transcriptional analysis further characterized thetazgene cluster to consist of 16 genes with the NR-PKS and the HR-PKS collaborating in a convergent mode. Based on the putative gene functions and the characterized compounds structural information, a biosynthetic pathway of azaterrilone A (1) was proposed.
丝状真菌的次生代谢产物是生物活性成分的重要来源。通过对土曲霉的基因组测序，发现了许多推测参与产生次生代谢产物的沉默次生代谢物生物合成基因簇。通过过表达途径特异性调节剂来激活沉默基因簇是发现新型真菌次生代谢产物的有效途径。用诱导型 Tet-on 系统替换途径特异性激活剂的天然启动子以激活 taz 途径，导致发现了一系列氮杂菲酮类次生代谢产物，其中 azaterrilone A（1）被首次分离和鉴定。核心 PKS 基因的遗传缺失和转录分析进一步表征了 taz 基因簇，该基因簇由 16 个基因组成，NR-PKS 和 HR-PKS 以收敛模式协同作用。基于假定的基因功能和特征化合物结构信息，提出了 azaterrilone A（1）的生物合成途径。
