BIOSYNTHESIS OF BETA LACTAM ANTIBIOTICS

β-内酰胺类抗生素是最重要的化疗药物之一。 在对抗人类的细菌感染方面。作为一个群体，他们构成了更多 占全球合乎道德的药品销售额的10%以上。成长中的化学和遗传 有信息表明，它们至少可以分为四个 生物合成课程。这些群体呈现出独特而耐人寻味的 体内提供张力环系统任务的酶解方法 具有很高的化学势和抑制特异性。生物合成 概述了化学、酶和遗传方面的研究。 理解(1)单环β-内酰胺形成的方法 诺卡菌素和单环菌胺，(2)重要的β-内酰胺酶的起源 缓蚀剂克拉维酸和相关的反足克拉维和，(3) 使用碳青霉烯-3-羧酸盐创建碳青霉烯核， 最简单的成员是40多种天然产品，如 实验系统。虽然对生物有机的基本兴趣问题 在这些研究中将涉及化学，有价值的知识可以 从而提高了这些重要商品的产量， 例如，通过合并密钥的多个副本 商业发酵菌株中生物合成基因的可能用途 固定化酶或其定点突变体在合成或 修改，以及改进的结构类型的发展 对耐药菌株的抑菌活性。

The beta-lactam antibiotics are among the foremost chemotherapeutic agents in combatting bacterial infections in man. As a group they constitute more than 10% of ethical drug sales world-wide. Growing chemical and genetic information suggests that they can be divided into at least four biosynthetic classes. These groups present distinct and intriguing enzymatic solutions to the in vivo task of providing strained ring systems of high chemical potential and inhibitory specificity. Biosynthetic investigations are outlined relying on chemical, enzymatic and genetic methods to understand (1) monocyclic beta-lactam formation evident in the nocardicins and monobactams, (2) genesis of the important beta-lactamase inhibitor clavulanic acid and the related, antipodal clavams and, (3) creation of the carbapenem nucleus using carbapenem-3-carboxylate, the simplest member a family of more than 40 natural products, as the experimental system. While questions of fundamental interest in bioorganic chemistry will be addressed in these studies, valuable knowledge can be gained that lead to improved production of these important commodities, for example, through the incorporation of multiple copies of key biosynthetic genes in commercial fermentation strains, the possible use of immobilized enzymes or their site-specific mutants in synthesis or modification, and the development of improved structural types conferring antiobiotic activity against resistant bacterial strains.