Rational Domain Swaps Decipher Programming in Fungal Highly Reducing Polyketide Synthases and Resurrect an Extinct Metabolite

被引：105

作者：

Fisch, Katja M. ^{[1
]}

Bakeer, Walid ^{[1
,2
]}

Yakasai, Ahmed A. ^{[1
]}

Song, Zhongshu ^{[1
]}

Pedrick, Jennifer ^{[1
]}

Wasil, Zahida ^{[1
]}

Bailey, Andrew M. ^{[3
]}

Lazarus, Colin M. ^{[3
]}

Simpson, Thomas J. ^{[1
]}

Cox, Russell J. ^{[1
]}

机构：

[1] Univ Bristol, Sch Chem, Bristol BS8 1TS, Avon, England

[2] Beni Suef Univ, Fac Pharm, Bani Suwayf 32514, Egypt

[3] Univ Bristol, Sch Biol Sci, Bristol BS8 1UG, Avon, England

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2011年 / 133卷 / 41期

基金：

英国生物技术与生命科学研究理事会; 英国工程与自然科学研究理事会;

关键词：

FATTY-ACID SYNTHASE; BEAUVERIA-BASSIANA; KETOSYNTHASE DOMAIN; 2-PYRIDONE TENELLIN; BIOSYNTHESIS; PROTEINS;

D O I：

10.1021/ja206914q

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

The mechanism of programming of iterative highly reducing polyketide synthases remains one of the key unsolved problems of secondary metabolism. We conducted rational domain swaps between the polyketide synthases encoding the biosynthesis of the closely related compounds tenellin and desmethylbassianin. Expression of the hybrid synthetases in Aspergillus oryzae led to the production of reprogrammed compounds in which the changes to the methylation pattern and chain length could be mapped to the domain swaps. These experiments reveal for the first time the origin of programming in these systems. Domain swaps combined with coexpression of two cytochrome P450 encoding genes from the tenellin biosynthetic gene cluster led to the resurrection of the extinct metabolite bassianin.

引用

页码：16635 / 16641

页数：7

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