Greco Claudio, de Mattos-Shipley Kate, Bailey Andrew M, Mulholland Nicholas P, Vincent Jason L, Willis Christine L, Cox Russell J, Simpson Thomas J
School of Chemistry , University of Bristol , Cantock's Close , Bristol , UK BS8 1TS . Email:
School of Biological Sciences , 24 Tyndall Avenue , Bristol , BS8 1TQ , UK.
Chem Sci. 2019 Jan 21;10(10):2930-2939. doi: 10.1039/c8sc05126g. eCollection 2019 Mar 14.
Three novel dimeric xanthones, cryptosporioptides A-C were isolated from sp. 8999 and their structures elucidated. Methylation of cryptosporioptide A gave a methyl ester with identical NMR data to cryptosporioptide, a compound previously reported to have been isolated from the same fungus. However, HRMS analysis revealed that cryptosporioptide is a symmetrical dimer, not a monomer as previously proposed, and the revised structure was elucidated by extensive NMR analysis. The genome of sp. 8999 was sequenced and the dimeric xanthone () biosynthetic gene cluster responsible for the production of the cryptosporioptides was identified. Gene disruption experiments identified a gene () encoding a cytochrome P450 oxygenase as being responsible for the dimerisation step late in the biosynthetic pathway. Disruption of led to the isolation of novel monomeric xanthones. Cryptosporioptide B and C feature an unusual ethylmalonate subunit: a hrPKS and acyl CoA carboxylase are responsible for its formation. Bioinformatic analysis of the genomes of several fungi producing related xanthones, the widely occurring ergochromes, and related metabolites allows detailed annotation of the biosynthetic genes, and a rational overall biosynthetic scheme for the production of fungal dimeric xanthones to be proposed.
从菌株8999中分离出三种新型二聚口山酮类化合物，隐孢子虫素A - C，并阐明了它们的结构。隐孢子虫素A甲基化后得到一种甲酯，其核磁共振数据与隐孢子虫素相同，隐孢子虫素是一种先前报道从同一真菌中分离得到的化合物。然而，高分辨质谱分析表明，隐孢子虫素是一种对称二聚体，而非先前认为的单体，通过广泛的核磁共振分析阐明了其修正结构。对菌株8999的基因组进行了测序，并鉴定出负责隐孢子虫素产生的二聚口山酮（）生物合成基因簇。基因破坏实验确定了一个编码细胞色素P450加氧酶的基因（）是生物合成途径后期二聚化步骤的原因。破坏该基因导致分离出新型单体口山酮。隐孢子虫素B和C具有一个不寻常的乙基丙二酸亚基：一个hrPKS和酰基辅酶A羧化酶负责其形成。对几种产生相关口山酮的真菌、广泛存在的麦角色素及相关代谢产物的基因组进行生物信息学分析，有助于对生物合成基因进行详细注释，并提出真菌二聚口山酮产生的合理总体生物合成方案。
