Abstract Cytochalasins are a group of fungal secondary metabolites with diverse structures and bioactivities, including chaetoglobosin A production. Chaetoglobosin A is produced by Chaetomium globosum and has potential antifungal activity. Bioinformatics analysis of the chaetoglobosin A gene cluster (che) showed it that consists of nine open reading frames, including those encoding polyketide synthases (PKSs), PKS extender units, post-PKS modifications, and proposed regulators. Here, the role of the CgcheR regulator was investigated using gene disruption experiments. The CgcheR disruptant (ΔCgcheR) completely abolished the production of chaetoglobosin A, which was restored by the introduction of a copy of the wild-type CgcheR gene, suggesting that CgcheR is involved in chaetoglobosin A biosynthesis. A transcriptional analysis of the CgcheR disruptant indicated that CgCheR activates the transcription of chaetoglobosin biosynthetic genes in a pathway-specific manner. Furthermore, constitutive overexpression of CgcheR significantly improved the production of chaetoglobosin A from 52 to 260 mg/L. Surprisingly, CgcheR also played a critical role in sporulation; the CgcheR disruptant lost the ability to produce spores, suggesting that the regulator modulates cellular development. Our results not only shed light on the regulation of chaetoglobosin A biosynthesis, but also indicate a relationship between secondary metabolism and fungal morphogenesis.

中文翻译：

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球毛壳菌中毛壳球蛋白 A 生物合成调节剂的功能分析

摘要 细胞松弛素是一组具有多种结构和生物活性的真菌次级代谢产物，包括毛壳球蛋白 A 的产生。Chaetoglobosin A 由 Chaetomium globosum 产生，具有潜在的抗真菌活性。chaetoglobosin A 基因簇 (che) 的生物信息学分析表明，它由 9 个开放阅读框组成，包括编码聚酮合酶 (PKS)、PKS 扩展单元、PKS 后修饰和提议的调节器的那些。在这里，使用基因破坏实验研究了 CgcheR 调节器的作用。CgcheR 破坏子 (ΔCgcheR) 完全消除了 chaetoglobosin A 的产生，通过引入野生型 CgcheR 基因的拷贝恢复了这种产生，表明 CgcheR 参与了 chaetoglobosin A 的生物合成。CgcheR 干扰物的转录分析表明，CgCheR 以特定途径激活毛壳球蛋白生物合成基因的转录。此外，CgcheR 的组成型过表达显着提高了 chaetoglobosin A 的产量，从 52 到 260 mg/L。令人惊讶的是，CgcheR 在孢子形成中也发挥了关键作用。CgcheR 破坏剂失去了产生孢子的能力，这表明调节剂调节细胞发育。我们的结果不仅阐明了毛珠蛋白 A 生物合成的调节，而且还表明了次级代谢与真菌形态发生之间的关系。CgcheR 的组成型过表达显着提高了 chaetoglobosin A 的产量，从 52 到 260 mg/L。令人惊讶的是，CgcheR 在孢子形成中也发挥了关键作用。CgcheR 破坏剂失去了产生孢子的能力，这表明调节剂调节细胞发育。我们的结果不仅阐明了毛珠蛋白 A 生物合成的调节，而且还表明了次级代谢与真菌形态发生之间的关系。CgcheR 的组成型过表达显着提高了 chaetoglobosin A 的产量，从 52 到 260 mg/L。令人惊讶的是，CgcheR 在孢子形成中也发挥了关键作用。CgcheR 破坏剂失去了产生孢子的能力，这表明调节剂调节细胞发育。我们的结果不仅阐明了毛珠蛋白 A 生物合成的调节，而且还表明了次级代谢与真菌形态发生之间的关系。