Directed evolution experiments reveal mutations at cycloartenol synthase residue His477 that dramatically alter catalysis

被引：39

作者：

Segura, MJR

Lodeiro, S

Meyer, MM

Patel, AJ

Matsuda, SPT ^{[1
]}

机构：

[1] Rice Univ, Dept Chem, Houston, TX 77005 USA

[2] Rice Univ, Dept Biochem & Cell Biol, Houston, TX 77005 USA

来源：

ORGANIC LETTERS | 2002年 / 4卷 / 25期

关键词：

D O I：

10.1021/ol0269897

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

[GRAPHICS] Cycloartenol synthase cyclizes and rearranges oxidosqualene to the protosteryl cation and then specifically deprotonates from C-19. To identify mutants that deprotonate differently, randomly generated mutant cycloartenol synthases were selected in a yeast lanosterol synthase mutant. A novel His477Asn mutant was uncovered that produces 88% lanosterol and 12% parkeol. The His477Gln mutant produces 73% parkeol, 22% lanosterol, and 5% Delta(7)-lanosterol. These are the most accurate lanosterol synthase and parkeol synthase that have been generated by mutagenesis.

引用

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页码：4459 / 4462

页数：4

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