A plant type III polyketide synthase that produces pentaketide chromone

被引:95
作者
Abe, I [1 ]
Utsumi, Y
Oguro, S
Morita, H
Sano, Y
Noguchi, H
机构
[1] Univ Shizuoka, Sch Pharmaceut Sci, Shizuoka 4228526, Japan
[2] Univ Shizuoka, Program COE 21, Shizuoka 4228526, Japan
关键词
D O I
10.1021/ja0431206
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
A novel plant-specific type III polyketide synthase (PKS) that catalyzes formation of a pentaketide chromone, 5,7-dihydroxy-2-methylchromone, from five molecules of malonyl-CoA, was cloned and sequenced from aloe (Aloe arborescens). Site-directed mutagenesis revealed that Met207 (corresponding to Thr197 in CHS) determines the polyketide chain length and the product specificity of the enzyme; remarkably, replacement of a single amino acid residue, Met207, with Gly yielded a mutant enzyme that efficiently produces aromatic octaketides, SEK4 and SEK4b, the products of the minimal PKS for actinorhodin (act from Streptomyces coelicolor), from eight molecules of malonyl-CoA. This provided new insights into the catalytic functions and specificities of the CHS-superfamily type III PKS enzymes. Copyright © 2005 American Chemical Society.
引用
收藏
页码:1362 / 1363
页数:2
相关论文
共 37 条
[1]   Benzalacetone synthase -: A novel polyketide synthase that plays a crucial role in the biosynthesis of phenylbutanones in Rheum palmatum [J].
Abe, I ;
Takahashi, Y ;
Morita, H ;
Noguchi, H .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 2001, 268 (11) :3354-3359
[2]   Enzymatic formation of long-chain polyketid pyrones by plant type III polyketide synthases [J].
Abe, I ;
Watanabe, T ;
Noguchi, H .
PHYTOCHEMISTRY, 2004, 65 (17) :2447-2453
[3]   The first plant type III polyketide synthase that catalyzes formation of aromatic heptaketide [J].
Abe, I ;
Utsumi, Y ;
Oguro, S ;
Noguchi, H .
FEBS LETTERS, 2004, 562 (1-3) :171-176
[4]   Site-directed mutagenesis of benzalacetone synthase -: The role of PHE215 in plant type III polyketide synthases [J].
Abe, I ;
Sano, Y ;
Takahashi, Y ;
Noguchi, H .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (27) :25218-25226
[5]   Enzymatic formation of unnatural novel polyketides from alternate starter and nonphysiological extension substrate by chalcone synthase [J].
Abe, I ;
Takahashi, Y ;
Lou, WW ;
Noguchi, H .
ORGANIC LETTERS, 2003, 5 (08) :1277-1280
[6]   Enzymatic formation of an unnatural C6-C5 aromatic polyketide by plant type III polyketide synthases [J].
Abe, I ;
Takahashi, Y ;
Noguchi, H .
ORGANIC LETTERS, 2002, 4 (21) :3623-3626
[7]   Substrate specificity of chalcone synthase: Enzymatic formation of unnatural polyketides from synthetic cinnamoyl-CoA analogues [J].
Abe, I ;
Morita, H ;
Nomura, A ;
Noguchi, H .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2000, 122 (45) :11242-11243
[8]   Crystal structure of a bacterial type III polyketide synthase and enzymatic control of reactive polyketide intermediates [J].
Austin, MB ;
Izumikawa, M ;
Bowman, ME ;
Udwary, DW ;
Ferrer, JL ;
Moore, BS ;
Noel, JP .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (43) :45162-45174
[9]   An aldol switch discovered in stilbene synthases mediates cyclization specificity of type III polyketide synthases [J].
Austin, MB ;
Bowman, ME ;
Ferrer, JL ;
Schröder, J ;
Noel, JP .
CHEMISTRY & BIOLOGY, 2004, 11 (09) :1179-1194
[10]   The chalcone synthase superfamily of type III polyketide synthases [J].
Austin, MB ;
Noel, JP .
NATURAL PRODUCT REPORTS, 2003, 20 (01) :79-110