Lodeiro Silvia, Xiong Quanbo, Wilson William K, Ivanova Yulia, Smith McKenzie L, May Gregory S, Matsuda Seiichi P T
Department of Chemistry, Rice University, Houston, Texas 77005, USA.
Org Lett. 2009 Mar 19;11(6):1241-4. doi: 10.1021/ol802696a.
Details of the fungal biosynthetic pathway to helvolic acid and other fusidane antibiotics remain obscure. During product characterization of oxidosqualene cyclases in Aspergillus fumigatus, we found the long-sought cyclase that makes (17Z)-protosta-17(20),24-dien-3beta-ol, the precursor of helvolic acid. We then identified a gene cluster encoding the pathway to helvolic acid, which is controlled by a transcription regulator (LaeA) associated with fungal virulence. Evidence regarding the evolutionary origin and taxonomic distribution of fusidane biosynthesis is also presented.
真菌生物合成途径生成戊霉素酸及其他夫西地烷类抗生素的具体细节仍不清楚。在烟曲霉氧化鲨烯环化酶的产物表征过程中,我们发现了长期以来一直在寻找的环化酶,该酶能生成戊霉素酸的前体(17Z)-原托-17(20),24-二烯-3β-醇。然后,我们鉴定出一个编码戊霉素酸生物合成途径的基因簇,该途径受与真菌毒力相关的转录调节因子(LaeA)控制。文中还提供了有关夫西地烷生物合成的进化起源和分类分布的证据。