Novel inhibitors of the condensing enzymes of the Type II fatty acid synthase of pea (Pisum sativum)

被引:38
作者
Jones, AL
Herbert, D
Rutter, AJ
Dancer, JE
Harwood, JL
机构
[1] Univ Wales Coll Cardiff, Cardiff Sch Biosci, Cardiff CF10 3US, S Glam, Wales
[2] AgrEvo UK Ltd, Saffron Walden CB10 1XL, Essex, England
基金
英国医学研究理事会;
关键词
thiolactomycin analogues; plant fatty acid synthesis;
D O I
10.1042/0264-6021:3470205
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 type II fatty acid synthases (FASs) of higher plants (and Escherichia coli) contain three condensing enzymes called beta-ketoacyl-ACP synthases (KAS), where ACP is acyl-carrier-protein. We have used novel derivatives of the antibiotic thiolactomycin to inhibit these enzymes. Overall de novo fatty acid biosynthesis was measured using [1-C-14]acetate substrate and chloroplast preparations from pea leaves, and [1-C-14]laurate was used to distinguish between the effects of the inhibitors on KAS I from those on KAS II. In addition, the activities of these enzymes, together with the short-chain condensing enzyme, KAS III, were measured directly. Six analogues were tested and two, both with extended hydrocarbon side chains, were found to be more effective inhibitors than thiolactomycin. Incubations with chloroplasts and direct assay of the individual condensing enzymes showed that all three compounds inhibited the pea FAS condensing enzymes in the order KAS II > KAS I > KAS III. These results demonstrate the general activity of thiolactomycin and its derivatives against these FAS condensation reactions, and suggest that such compounds will be useful for further detailed studies of inhibition and for use as pharmaceuticals against Type II FASs of pathogens.
引用
收藏
页码:205 / 209
页数:5
相关论文
共 29 条
[1]   COPPER ENZYMES IN ISOLATED CHLOROPLASTS - POLYPHENOLOXIDASE IN BETA-VULGARIS [J].
ARNON, DI .
PLANT PHYSIOLOGY, 1949, 24 (01) :1-15
[2]  
Cho S, 1987, METABOLISM STRUCTURE, P623
[3]  
GARBUS J, 1963, J BIOL CHEM, V238, P59
[4]   ACETOACYL-ACYL CARRIER PROTEIN SYNTHASE FROM AVOCADO - ITS PURIFICATION, CHARACTERIZATION AND CLEAR RESOLUTION FROM ACETYL COA-ACP TRANSACYLASE [J].
GULLIVER, BS ;
SLABAS, AR .
PLANT MOLECULAR BIOLOGY, 1994, 25 (02) :179-191
[5]   Recent advances in the biosynthesis of plant fatty acids [J].
Harwood, JL .
BIOCHIMICA ET BIOPHYSICA ACTA-LIPIDS AND LIPID METABOLISM, 1996, 1301 (1-2) :7-56
[6]   FATTY-ACID METABOLISM [J].
HARWOOD, JL .
ANNUAL REVIEW OF PLANT PHYSIOLOGY AND PLANT MOLECULAR BIOLOGY, 1988, 39 :101-138
[7]   PARTIAL SEPARATION OF INDIVIDUAL ENZYME-ACTIVITIES OF AN ACP-DEPENDENT FATTY-ACID SYNTHETASE FROM BARLEY CHLOROPLASTS [J].
HOJ, PB ;
MIKKELSEN, JD .
CARLSBERG RESEARCH COMMUNICATIONS, 1982, 47 (02) :119-141
[8]  
JACKOWSKI S, 1987, J BIOL CHEM, V262, P7927
[9]   A CERULENIN INSENSITIVE SHORT CHAIN 3-KETOACYL-ACYL CARRIER PROTEIN SYNTHASE IN SPINACIA-OLERACEA LEAVES [J].
JAWORSKI, JG ;
CLOUGH, RC ;
BARNUM, SR .
PLANT PHYSIOLOGY, 1989, 90 (01) :41-44
[10]  
JAWORSKI JG, 1990, PLANT LIPID BIOCHEMISTRY, STRUCTURE AND UTILIZATION, P97