Unprecedented mechanism of chain length determination in fungal aromatic polyketide synthases

被引:36
作者
Watanabe, A [1 ]
Ebizuka, Y [1 ]
机构
[1] Univ Tokyo, Sch Pharmaceut Sci, Bunkyo Ku, Tokyo 1130033, Japan
来源
CHEMISTRY & BIOLOGY | 2004年 / 11卷 / 08期
基金
日本学术振兴会;
关键词
D O I
10.1016/j.chembiol.2004.05.015
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
Fungal aromatic polyketides show remarkable structural diversity fundamentally derived from variations in chain length and cyclization pattern. Their basic skeletons are synthesized by multifunctional iterative type I polyketide synthases (PKSs). Recently, we have found that the C-terminal thioesterase (TE)-like domain of Aspergillus nidulans WA catalyzes Claisen-type cyclization to form the B-ring of naphthopyrone YWA1. Here we report the unprecedented mechanism of chain length determination by the C-terminal TE-like domain of Colletotrichum lagenarium PKS1, which, in addition to catalyzing Claisen-type cyclization, intercepts the polyketomethylene intermediate from the acyl carrier protein domain during the condensation reaction to produce shorter chain length products. This chain length determination system is novel among PKSs, including bacterial and plant PKSs. The functional diversity of the TE-like domain directly influences the structural diversity of aromatic polyketides in C. lagenarium, PKS1.
引用
收藏
页码:1101 / 1106
页数:6
相关论文
共 24 条
[1]   The chalcone synthase superfamily of type III polyketide synthases [J].
Austin, MB ;
Noel, JP .
NATURAL PRODUCT REPORTS, 2003, 20 (01) :79-110
[2]   THE MULTIFUNCTIONAL 6-METHYLSALICYLIC ACID SYNTHASE GENE OF PENICILLIUM-PATULUM - ITS GENE STRUCTURE RELATIVE TO THAT OF OTHER POLYKETIDE SYNTHASES [J].
BECK, J ;
RIPKA, S ;
SIEGNER, A ;
SCHILTZ, E ;
SCHWEIZER, E .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 1990, 192 (02) :487-498
[3]   A chain initiation factor common to both modular and aromatic polyketide synthases [J].
Bisang, C ;
Long, PF ;
Cortés, J ;
Westcott, J ;
Crosby, J ;
Matharu, AL ;
Cox, RJ ;
Simpson, TJ ;
Staunton, J ;
Leadlay, PF .
NATURE, 1999, 401 (6752) :502-505
[4]   Structure of chalcone synthase and the molecular basis of plant polyketide biosynthesis [J].
Ferrer, JL ;
Jez, JM ;
Bowman, ME ;
Dixon, RA ;
Noel, JP .
NATURE STRUCTURAL BIOLOGY, 1999, 6 (08) :775-784
[5]   Cloning of the polyketide synthase gene atX from Aspergillus terreus and its identification as the 6-methylsalicylic acid synthase gene by heterologous expression [J].
Fujii, I ;
Ono, Y ;
Tada, H ;
Gomi, K ;
Ebizuka, Y ;
Sankawa, U .
MOLECULAR AND GENERAL GENETICS, 1996, 253 (1-2) :1-10
[6]   Heterologous expression and product identification of Colletotrichum lagenarium polyketide synthase encoded by the PKS1 gene involved in melanin biosynthesis [J].
Fujii, I ;
Mori, Y ;
Watanabe, A ;
Kubo, Y ;
Tsuji, G ;
Ebizuka, Y .
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 1999, 63 (08) :1445-1452
[7]   Identification of Claisen cyclase domain in fungal polyketide synthase WA, a naphthopyrone synthase of Aspergillus nidulans [J].
Fujii, I ;
Watanabe, A ;
Sankawa, U ;
Ebizuka, Y .
CHEMISTRY & BIOLOGY, 2001, 8 (02) :189-197
[8]  
Fujii I., 2002, Mycotoxins, V52, P135, DOI 10.2520/myco.52.135
[9]   CLONING AND NUCLEOTIDE-SEQUENCE OF THE RIBONUCLEASE T-1 GENE (RNTA) FROM ASPERGILLUS-ORYZAE AND ITS EXPRESSION IN SACCHAROMYCES-CEREVISIAE AND ASPERGILLUS-ORYZAE [J].
FUJII, T ;
YAMAOKA, H ;
GOMI, K ;
KITAMOTO, K ;
KUMAGAI, C .
BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY, 1995, 59 (10) :1869-1874
[10]  
GOMI K, 1987, BIOSCI BIOTECH BIOCH, V59, P1869