丝状真菌次级代谢产物生物合成表观遗传调控.pdf

生 物 工 程 学 报 Chin J Biotech 2011, August 25; 27(8): 1142−1148 journals.im.ac.cn Chinese Journal of Biotechnology ISSN 1000-3061 cjb@im.ac.cn ©2011 CJB, All rights reserved. 综 述 丝状真菌次级代谢产物生物合成的表观遗传调控 周锐，廖国建，胡昌华 400716 摘 要: 丝状真菌产生的次级代谢产物是新药的重要来源之一，其生物合成过程受到众多因素的调控。最近的研究表 明，表观遗传对多种丝状真菌次级代谢产物的生物合成具有调控作用。DNA 和组蛋白的甲基化与乙酰化修饰是目前所 知的丝状真菌主要的表观遗传调控形式。通过过表达或缺失相关表观修饰基因和利用小分子表观遗传试剂改变丝状真 菌染色体的修饰形式，不仅可以提高多种已知次级代谢产物产量，而且可以通过激活沉默的生物合成基因簇诱导丝状 真菌产生新的未知代谢产物。丝状真菌表观遗传学正逐渐成为真菌菌株改良的新策略以及挖掘真菌次级代谢产物合成 潜力的强有力手段。 关键词: 丝状真菌，表观遗传，DNA 甲基化，组蛋白修饰，次级代谢产物，生物合成，菌株改良 Epigenetic regulation of secondary metabolite biosynthesis in filamentous fungi: a review Rui Zhou, Guojian Liao, and Changhua Hu Institute of Modern Biopharmaceuticals , School of Pharmaceutical Sciences, Southwest University, Chongqing 400716, China Abstract: Secondary metabolites of filamentous fungi are important sources of new drugs, and their biosynthetic processes are regulated by numerous factors. Recent studies indicate that many filamentous fungal secondary metabolites are regulated by epigenetic modifications, which not only affect the titers of secondary metabolites, but also activate the cryptic gene clusters. This review summarizes recent advances of epigenetic application in filamentous fungal secondary metabolite biosynthesis, especially the types of fungal epigenetic modification and epigenetic remodeling of the fungal secondary metabolism. The application of epigenetic theory in filamentous fungi is becoming a new strategy for fungal strain improvement and a powerful method to obtain novel natural products. Keywords: filamentous fungi, epigenetic, DNA methylation, histone modification, secondary metabolite, biosynthesis,