Enzymatic formation of multiple triterpenes by mutation of tyrosine 510 of the oxidosqualene-lanosterol cyclase from Saccharomyces cerevisiae

被引：33

作者：

Wu, TK ^{[1
]}

Chang, CH ^{[1
]}

机构：

[1] Natl Chiao Tung Univ, Ctr Interdisciplinary Mol Sci, Dept Biol Sci & Technol, Hsinchu 300, Taiwan

来源：

CHEMBIOCHEM | 2004年 / 5卷 / 12期

关键词：

cyclization; mutagenesis; plasmid shuffle; sterols; terpenoids;

D O I：

10.1002/cbic.200400079

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The simultaneous formation of monocyclic and differentially deprotonated triterpenes by mutation of Tyr510 of the oxidosqualene-lanosterol cyclase (ERG7) from Saccharomyces cerevisiae is reported (see scheme). Possible dual functions of this residue involved in the cyclization and deprotonation steps of the oxidosqualene cyclization/rearrangement cascade are discussed.

引用

页码：1712 / 1715

页数：4

共 23 条

[1] ENZYMATIC CYCLIZATION OF SQUALENE AND OXIDOSQUALENE TO STEROLS AND TRITERPENES [J].

ABE, I ;

ROHMER, M ;

PRESTWICH, GD .

CHEMICAL REVIEWS, 1993, 93 (06) :2189-2206

[2] Camelliols A-C, three novel incompletely cyclized triterpene alcohols from sasanqua oil (Camellia sasanqua) [J].

Akihisa, T ;

Arai, K ;

Kimura, Y ;

Koike, K ;

Kokke, WCMC ;

Shibata, T ;

Nikaido, T .

JOURNAL OF NATURAL PRODUCTS, 1999, 62 (02) :265-268

[3] Studies on the substrate binding segments and catalytic action of lanosterol synthase. Affinity labeling with carbocations derived from mechanism-based analogs of 2,3-oxidosqualene and site-directed mutagenesis probes [J].

Corey, EJ ;

Cheng, HM ;

Baker, CH ;

Matsuda, SPT ;

Li, D ;

Song, XL .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1997, 119 (06) :1289-1296

[4] Site-directed mutagenesis of squalene-hopene cyclase: altered substrate specificity and product distribution [J].

Dang, TY ;

Prestwich, GD .

CHEMISTRY & BIOLOGY, 2000, 7 (08) :643-649

[5] Directed evolution to investigate steric control of enzymatic oxidosqualene cyclization. An isoleucine-to-valine mutation in cycloartenol synthase allows lanosterol and parkeol biosynthesis [J].

Hart, EA ;

Hua, L ;

Darr, LB ;

Wilson, WK ;

Pang, JH ;

Matsuda, SPT .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1999, 121 (42) :9887-9888

[6] A tyrosine-to-threonine mutation converts cycloartenol synthase to an oxidosqualene cyclase that forms lanosterol as its major product [J].

Herrera, JBR ;

Wilson, WK ;

Matsuda, SPT .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2000, 122 (28) :6765-6766

[7] Steric bulk at position 454 in Saccharomyces cerevisiae lanosterol synthase influences B-ring formation but not deprotonation [J].

Joubert, BM ;

Hua, L ;

Matsuda, SPT .

ORGANIC LETTERS, 2000, 2 (03) :339-341

[8] Trypanosome and animal lanosterol synthases use different catalytic motifs [J].

Joubert, BM ;

Buckner, FS ;

Matsuda, SPT .

ORGANIC LETTERS, 2001, 3 (12) :1957-1960

[9] β-Amyrin synthase -: Cloning of oxidosqualene cyclase that catalyzes the formation of the most popular triterpene among higher plants [J].

Kushiro, T ;

Shibuya, M ;

Ebizuka, Y .

EUROPEAN JOURNAL OF BIOCHEMISTRY, 1998, 256 (01) :238-244

[10] Mutational studies on triterpene syntheses:: Engineering lupeol synthase into β-amyrin synthase [J].

Kushiro, T ;

Shibuya, M ;

Masuda, K ;

Ebizuka, Y .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2000, 122 (29) :6816-6824

← 1 2 3 →