摘要
人类对放线菌药物(特别是抗生素)开发取得了极其辉煌的成就,为人类的健康事业做出了巨大贡献。与其它天然药物开发一样,当今要再从放线菌开发新药是越来越困难了。本文以新思维、新方法、新菌种、新基因、新产物、新用途为指导思想,提出了一个放线菌药物研究开发的新程序,并阐明了该程序的出发点、关键点及优点,对天然药物开发新技术的研究进展做了预测和展望。
Development of pharmaceuticals, specially antibiotics, from Actinomycetes have been obtained refulgent achievements, and make huge contribution for human health. Alike with development of other natural drug, the development of pharmaceuticals from Actinomycetes is very difficult now. One of the difficulties is eliminating about 5,000 known Actinomycete species and 30,000 natural products, which leads to prolong the developmental periods and increase cost. Authors put forward a new approach on research and development of pharmaceuticals from Actinomycetes based on new thinking, technology, species, gene, products and use for meeting these difficulties. First, collecting test samples from primeval and extreme environments, sea, animal and plant. Second, ceaselessly designing, improving and perfecting the isolation procedures of Actinomycetes for obtaining more and more unknown strains. Third, 98.5 % of similarity of 16S rDNA sequence as a circumscription of possible novel species, and the new species as source of research work. Fourth, about 8 media are used for fermentation of the new species for producing potential metabolites as much as possible. Fifth, the ferments are extracted by solid phase, eluted by 10 polar grads of organic reagents respectively and detected by HPLC or LC-Mass, the chromatography is inputted data base, and the interesting fractions will be discovered. Sixth, after obtained new chemicals, the biosynthesis gene cluster of the chemicals will be sequenced. Then new, high active and perfect chemicals as the leader compounds will obtain by using combinatorial biosynthesis and gene shuffling etc. for future development.
基金
本研究受国家重大基础研究发展规划项目(项目编号:2004CB719601),国家科技部重点国际合作项目(项目编号:2006DFA3]550)资助,特此致谢.
关键词
药物开发
放线菌
pharmaceutical development
Actinomycetes
new approach