CLUSTERS OF GENES FOR THE BIOSYNTHESIS OF ANTIBIOTICS - REGULATORY GENES AND OVERPRODUCTION OF PHARMACEUTICALS

被引:37
作者
MARTIN, JF
机构
[1] Section of Microbiology, Department of Ecology, Genetics and Microbiology, Faculty of Biology, University of León, León
来源
JOURNAL OF INDUSTRIAL MICROBIOLOGY | 1992年 / 9卷 / 02期
关键词
BETA-LACTAM ANTIBIOTICS; PENICILLIN; CEPHALOSPORIN; CEPHAMYCIN; BIOSYNTHETIC GENE CLUSTERS; CONTROL OF EXPRESSION;
D O I
10.1007/BF01569737
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
In the last decade numerous genes involved in the biosynthesis of antibiotics, pigments, herbicides and other secondary metabolites have been cloned. The genes involved in the biosynthesis of penicillin, cephalosporin and cephamycins are organized in clusters as occurs also with the biosynthetic genes of other antibiotics and secondary metabolites (see review by Martin and Liras [65]). We have cloned genes involved in the biosynthesis of beta-lactam antibiotics from five different beta-lactam producing organisms both eucaryotic (Penicillium chrysogenum, Cephalosporium acremonium (syn. Acremonium chrysogenum) Aspergillus nidulans) and procaryotic (Nocardia lactamdurans, Streptomyces clavuligerus). In P. chrysogenum and A. nidulans the organization of the pcbAB, pcbC and penDE genes for ACV synthetase, IPN synthase and IPN acyltransferase showed a similar arrangement. In A. chrysogenum two different clusters of genes have been cloned. The cluster of early genes encodes ACV synthetase and IPN synthase, whereas the cluster of late genes encodes deacetoxycephalosporin C synthetase/hydroxylase and deacetylcephalosporin C acetyltransferase. In N. lactamdurans and S. clavuligerus a cluster of early cephamycin genes has been fully characterized. It includes the lat (for lysine-6-aminotransferase), pcbAB (for ACV synthase) and pcbC (for IPN synthase) genes. Pathway-specific regulatory genes which act in a positive (or negative) form are associated with clusters of genes involved in antibiotic biosynthesis. In addition, widely acting positive regulatory elements exert a pleiotropic control on secondary metabolism and differentiation of antibiotic producing microorganisms. The application of recombinant DNA techniques will contribute significantly to the improvement of fermentation organisms.
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页码:73 / 90
页数:18
相关论文
共 99 条
[51]  
JENSEN SE, 1988, FEMS MICROBIOL LETT, V49, P213
[52]  
KERN BA, 1980, ANTIMICROB AGENTS CH, V17, P676
[53]   GENETIC DETERMINATION OF METHYLENOMYCIN SYNTHESIS BY SCP1 PLASMID OF STREPTOMYCES-COELICOLOR A3(2) [J].
KIRBY, R ;
HOPWOOD, DA .
JOURNAL OF GENERAL MICROBIOLOGY, 1977, 98 (JAN) :239-252
[54]  
KRATZSCHMAR J, 1989, J BACTERIOL, V171, P5422
[55]   PURIFICATION AND CHARACTERIZATION OF THE ISOPENICILLIN-N EPIMERASE FROM NOCARDIA-LACTAMDURANS [J].
LAIZ, L ;
LIRAS, P ;
CASTRO, JM ;
MARTIN, JF .
JOURNAL OF GENERAL MICROBIOLOGY, 1990, 136 :663-671
[56]  
LIRAS P, 1988, USE RECOMBINANT DNA, P217
[57]   ISOLATION AND NATURE OF INTRACELLULAR PEPTIDES FROM A CEPHALOSPORIN C-PRODUCING CEPHALOSPORIUM SP [J].
LODER, PB ;
ABRAHAM, EP .
BIOCHEMICAL JOURNAL, 1971, 123 (03) :471-&
[58]   CHARACTERIZATION OF THE BIOSYNTHESIS INVIVO OF ALPHA-AMINOADIPYL-CYSTEINYL-VALINE IN PENICILLIUM-CHRYSOGENUM [J].
LOPEZNIETO, MJ ;
RAMOS, FR ;
LUENGO, JM ;
MARTIN, JF .
APPLIED MICROBIOLOGY AND BIOTECHNOLOGY, 1985, 22 (05) :343-351
[59]   LYSINE CATABOLISM IN STREPTOMYCES SPP IS PRIMARILY THROUGH CADAVERINE - BETA-LACTAM PRODUCERS ALSO MAKE ALPHA-AMINOADIPATE [J].
MADDURI, K ;
STUTTARD, C ;
VINING, LC .
JOURNAL OF BACTERIOLOGY, 1989, 171 (01) :299-302
[60]   CLONING AND LOCATION OF A GENE GOVERNING LYSINE EPSILON-AMINOTRANSFERASE, AN ENZYME INITIATING BETA-LACTAM BIOSYNTHESIS IN STREPTOMYCES SPP. [J].
MADDURI, K ;
STUTTARD, C ;
VINING, LC .
JOURNAL OF BACTERIOLOGY, 1991, 173 (03) :985-988