Discovery and characterization of a cytochalasan biosynthetic cluster from the marine-derived fungusAspergillus flavipesCNL-338

被引：15
|
作者：
Heard, Stephanie C. [1 ]
Wu, Guangwei [1 ]
Winter, Jaclyn M. [1 ]
机构：
[1] Univ Utah, Coll Pharm, Dept Med Chem, Salt Lake City, UT 84112 USA
来源：
JOURNAL OF ANTIBIOTICS | 2020年 / 73卷 / 11期
关键词：
PEPTIDE SYNTHETASES; CONFERRING CODE; GENE-CLUSTER; CHAETOGLOBOSIN;
D O I：
10.1038/s41429-020-00368-0
中图分类号：
Q81 [生物工程学（生物技术）]; Q93 [微生物学];
学科分类号：
071005 ; 0836 ; 090102 ; 100705 ;
摘要：
Cytochalasans are a large family of well-studied cytotoxic molecules isolated from fungi. Investigation into the organic extract of the marine-derived fungal strainAspergillus flavipesCNL-338 led to the isolation of seven leucine-containing cytochalasans. Genome mining allowed for the identification of theffsbiosynthetic gene cluster, and genetic inactivation studies verified its involvement in cytochalasan biosynthesis. In addition, comparative analysis of key residues in the binding pocket of core cytochalasan biosynthetic enzymes revealed significant similarities among fungal adenylation domains despite differences in substrate preference. We report the identification of leucine-containing cytochalasans from the marine-derivedA. flavipesCNL-338 and the characterization of theffsbiosynthetic cluster as verified by genetic inactivation studies.
引用
收藏
页码：803 / 807
页数：5
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