State Key Laboratory of Ecological Pest Control for Fujian and Taiwan Crops, Key Laboratory of Pathogenic Fungi and Mycotoxins of Fujian Province, and School of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou, 350002, China.
Environ Microbiol. 2022 Mar;24(3):1340-1361. doi: 10.1111/1462-2920.15856. Epub 2021 Dec 8.
Myst family is highly conserved histone acetyltransferases in eukaryotic cells and is known to play crucial roles in various cellular processes; however, acetylation catalysed by acetyltransferases is unclear in filamentous fungi. Here, we identified two classical nonessential Myst enzymes and analysed their functions in Aspergillus flavus, which generates aflatoxin B1, one of the most carcinogenic secondary metabolites. MystA and MystB located in nuclei and cytoplasm, and mystA could acetylate H4K16ac, while mystB acetylates H3K14ac, H3K18ac and H3K23ac. Deletion mystA resulted in decreased conidiation, increased sclerotia formation and aflatoxin production. Deletion of mystB leads to significant defects in conidiation, sclerotia formation and aflatoxin production. Additionally, double-knockout mutant (ΔmystA/mystB) display a stronger and similar defect to ΔmystB mutant, indicating that mystB plays a major role in regulating development and aflatoxin production. Both mystA and mystB play important role in crop colonization. Moreover, catalytic domain MOZ and the catalytic site E199/E243 were important for the acetyltransferase function of Myst. Notably, chromatin immunoprecipitation results indicated that mystB participated in oxidative detoxification by regulating the acetylation level of H3K14, and further regulated nsdD to affect sclerotia formation and aflatoxin production. This study provides new evidences to discover the biological functions of histone acetyltransferase in A. flavus.
Myst 家族是真核细胞中高度保守的组蛋白乙酰转移酶，已知在各种细胞过程中发挥着关键作用；然而，丝状真菌中乙酰转移酶催化的乙酰化作用尚不清楚。在这里，我们鉴定了两个经典的非必需 Myst 酶，并分析了它们在产生黄曲霉毒素 B1（一种最具致癌性的次级代谢物之一）的黄曲霉中的功能。MystA 和 MystB 位于细胞核和细胞质中，并且 mystA 可以乙酰化 H4K16ac，而 mystB 乙酰化 H3K14ac、H3K18ac 和 H3K23ac。mystA 缺失导致分生孢子形成减少、产胞外多聚物增加和黄曲霉毒素产量增加。mystB 缺失导致分生孢子形成、产胞外多聚物和黄曲霉毒素产量显著缺陷。此外，双敲除突变体（ΔmystA/mystB）显示出比 ΔmystB 突变体更强和相似的缺陷，表明 mystB 在调节发育和黄曲霉毒素产生中起主要作用。mystA 和 mystB 在作物定殖中都发挥着重要作用。此外，MOZ 催化结构域和催化位点 E199/E243 对 Myst 的乙酰转移酶功能很重要。值得注意的是，染色质免疫沉淀结果表明，mystB 通过调节 H3K14 的乙酰化水平参与氧化解毒，并进一步调节 nsdD 影响产胞外多聚物和黄曲霉毒素的产生。本研究为发现黄曲霉中组蛋白乙酰转移酶的生物学功能提供了新的证据。
