Kieslich K
Arzneimittelforschung. 1986 Apr;36(4):774-8.
Before the advent of alchemy the therapeutic aids for man and animals consisted exclusively of using natural products in many different forms. Chemical syntheses have been used for little more than 100 years as a means of obtaining drugs. The discovery of penicillin and the first industrial production of this compound in 1941/42 opened the door to a third way for the preparation of drugs by exploitation of the manifold biosynthetic capabilities of microorganisms to produce antibiotics or more recently other pharmacologically active substances. The selective use of individual enzymatic transformation stages with microorganisms in chemical production pathways in particular by biotransformations of steroids in 1950 expanded the field of biotechnological production of pharmaceuticals. The increasing knowledge in the regulation of the biosynthesis of primary and secondary metabolites, the growing experience in the use of microorganisms as biocatalysts and source of valuable enzymes and the development of new economical technical procedures raised the number and volume of drugs prepared by microbial biosynthesis and biotransformation. The modern method of the genetic engineering supported by the chemical DNA-synthesis enabled the preparation of important proteohormones and physiologically active peptides in microorganisms. Finally, the development of monoclonal antibodies, although at present still formed in mammalian cells, will lead to new ways of therapy in future. A review is given on the present state of biotechnological productions of antibiotics, vitamins, steroids, alkaloids, amino acids and pharmaceutical enzymes combined with new developments in the preparation of blood factors, enzyme inhibitors, hormones and physiologically active peptides and the possible future use of monoclonal antibodies.
在炼金术出现之前,人类和动物的治疗辅助手段完全是使用多种不同形式的天然产物。化学合成作为获取药物的一种手段,其应用历史不过100多年。1941年/1942年青霉素的发现以及该化合物的首次工业化生产,开启了制备药物的第三条途径,即利用微生物多样的生物合成能力来生产抗生素,或者更近一些生产其他药理活性物质。特别是在1950年通过甾体的生物转化,在化学生产途径中对微生物的各个酶促转化阶段进行选择性利用,扩大了药物生物技术生产的领域。对初级和次级代谢产物生物合成调控的认识不断增加、将微生物用作生物催化剂和宝贵酶源的经验日益丰富以及新的经济技术程序的开发,提高了通过微生物生物合成和生物转化制备的药物的数量和产量。由化学DNA合成支持的现代基因工程方法,使得在微生物中制备重要的蛋白质激素和生理活性肽成为可能。最后,单克隆抗体的开发,尽管目前仍在哺乳动物细胞中产生,但未来将引领新的治疗方法。本文综述了抗生素、维生素、甾体、生物碱、氨基酸和药用酶的生物技术生产现状,以及血液因子、酶抑制剂、激素和生理活性肽制备方面的新进展,还有单克隆抗体未来可能的应用。