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抗生素生物合成的基因簇:调控基因与药物的过量生产

Clusters of genes for the biosynthesis of antibiotics: regulatory genes and overproduction of pharmaceuticals.

作者信息

Martin J F

机构信息

Department of Ecology, Genetics and Microbiology, Faculty of Biology, University of León, Spain.

出版信息

J Ind Microbiol. 1992 Feb-Mar;9(2):73-90. doi: 10.1007/BF01569737.

DOI:10.1007/BF01569737
PMID:1368054
Abstract

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 Martín 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.

摘要

在过去十年中,许多参与抗生素、色素、除草剂及其他次生代谢物生物合成的基因已被克隆。参与青霉素、头孢菌素和头霉素生物合成的基因成簇排列,其他抗生素和次生代谢物的生物合成基因也是如此(见Martín和Liras的综述[65])。我们已经从五种不同的β-内酰胺产生菌中克隆了参与β-内酰胺抗生素生物合成的基因,这些产生菌既有真核生物(产黄青霉、顶头孢霉(同义词:产黄头孢霉)、构巢曲霉),也有原核生物(耐乳糖诺卡氏菌、棒状链霉菌)。在产黄青霉和构巢曲霉中,用于ACV合成酶、异青霉素N合成酶和异青霉素N酰基转移酶的pcbAB、pcbC和penDE基因的排列方式相似。在产黄头孢霉中,已克隆了两个不同的基因簇。早期基因簇编码ACV合成酶和异青霉素N合成酶,而晚期基因簇编码去乙酰氧头孢菌素C合成酶/羟化酶和去乙酰头孢菌素C乙酰转移酶。在耐乳糖诺卡氏菌和棒状链霉菌中,一个早期头霉素基因簇已得到充分表征。它包括lat(赖氨酸-6-氨基转移酶)、pcbAB(ACV合成酶)和pcbC(异青霉素N合成酶)基因。以正(或负)形式起作用的途径特异性调控基因与参与抗生素生物合成的基因簇相关。此外,广泛作用的正调控元件对抗生素产生微生物的次生代谢和分化发挥多效性控制作用。重组DNA技术的应用将极大地有助于改良发酵生物。

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