Pinpointing pseurotins from a marine-derived Aspergillus as tools for chemical genetics using a synthetic lethality yeast screen

Pinpointing pseurotins from a marine-derived Aspergillus as tools for chemical genetics using a synthetic lethality yeast screen
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DOI:
10.1021/np070307c
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发表时间:
2007-10-01
影响因子:
5.1
通讯作者:
Crews, Phillip
Crews, Phillip
中科院分区:
生物学2区
文献类型:
--
作者:
Boot, Claudia M.;Gassner, Nadine C.;Crews, Phillip

文献摘要

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从海洋来源的烟曲霉中鉴定出混合聚酮合酶-非核糖体肽合成酶 (PKS/NRPS) 来源的新化合物 11-O-甲基伪锡 A (1)。使用酵母晕圈测定法对野生型和细胞周期相关的酿酒酵母突变株进行生物测定引导的分级分离,分离出 1,它选择性地抑制 Hof1 缺失菌株。包括 1D 和 2D NMR、HRESIMS、旋光度、J 分析和生物合成平行在内的技术被用于阐明 1 的平面结构和绝对构型。还分离出一种相关的已知化合物 pseurotin A (2),并发现在酵母筛选中没有活性。
A new compound of mixed polyketide synthase-nonribosomal peptide synthetase (PKS/NRPS) origin, 11-O-methylpseurotin A (1), was identified from a marine-derived Aspergillus fumigatus. Bioassay-guided fractionation using a yeast halo assay with wild-type and cell cycle-related mutant strains of Saccharomyces cerevisiae resulted in the isolation of 1, which selectively inhibited a Hof1 deletion strain. Techniques including 1D and 2D NMR, HRESIMS, optical rotation, J-based analysis, and biosynthetic parallels were used in the elucidation of the planar structure and absolute configuration of 1. A related known compound, pseurotin A (2), was also isolated and found to be inactive in the yeast screen.