Development of Genetic Dereplication Strains in Aspergillus nidulans Results in the Discovery of Aspercryptin

被引：153

作者：

Chiang, Yi-Ming ^{[1
,2
]}

Ahuja, Manmeet ^{[3
,7
]}

Oakley, C. Elizabeth ^{[3
]}

Entwistle, Ruth ^{[3
]}

Asokan, Anabanadam ^{[6
]}

Zutz, Christoph ^{[4
]}

Wang, Clay C. C. ^{[1
,5
]}

Oakley, Berl R. ^{[3
]}

机构：

[1] Univ So Calif, Sch Pharm, Dept Pharmacol & Pharmaceut Sci, Los Angeles, CA 90089 USA

[2] Chia Nan Univ Pharm & Sci, Dept Pharm, Tainan 71710, Taiwan

[3] Univ Kansas, Dept Mol Biosci, Lawrence, KS 66045 USA

[4] Univ Vet Med Vienna, Inst Milk Hyg, A-1210 Vienna, Austria

[5] Univ So Calif, Dept Chem, Los Angeles, CA 90089 USA

[6] Univ Kansas, Del Shankel Struct Biol Ctr, Lawrence, KS 66045 USA

[7] Reliance Ind Ltd, Reliance Technol Grp, Ind Biotechnol Div, Reliance Corp Pk,Thane Belapur Rd, Navi Mumbai 400701, India

来源：

ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2016年 / 55卷 / 05期

关键词：

aspergillus; biosynthesis; genetic dereplication; natural products; NRPS; FUNGAL SECONDARY METABOLISM; BIOSYNTHETIC-PATHWAY; FILAMENTOUS FUNGI; NATURAL-PRODUCTS; CLUSTERS; IDENTIFICATION; EXPRESSION; SYNTHASES; SYSTEM; FLAVUS;

D O I：

10.1002/anie.201507097

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

To reduce the secondary metabolite background in Aspergillus nidulans and minimize the rediscovery of compounds and pathway intermediates, we created a "genetic dereplication" strain in which we deleted eight of the most highly expressed secondary metabolite gene clusters (more than 244,000 base pairs deleted in total). This strain allowed us to discover a novel compound that we designate aspercryptin and to propose a biosynthetic pathway for the compound. Interestingly, aspercryptin is formed from compounds produced by two separate gene clusters, one of which makes the well-known product cichorine. This raises the exciting possibility that fungi use differential regulation of expression of secondary metabolite gene clusters to increase the diversity of metabolites they produce.

引用

页码：1662 / 1665

页数：4

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