微生物代谢物组ppt.ppt

Mining the Microbial Metabolome:a new frontier for natural productlead discovery Published on 《Drug Discovery Today》, 23 December 2003 By Natasa Peric-Concha and Paul F.Long The School of Pharmacy University of London 1.Background: 2.Traditional approaches to lead discovery The criteria for a successful screening library are hard to define, it is unlikely that any one screening library could possibly satisfy all such requirements. However, it is generally accepted that a screening library ought to contain as many unique structural entities as possible. Libraries that were synthesized via combinatorial chemistry approaches have,indeed,taken the pharmaceutical industry by storm since conception in the late 1980s. But unfortunately,the performance of such libraries has never reflected the initial promise. 4.Cryptic gene clusters revealed 基因簇 (gene clusters) 5. Harnessing the biosynthetic potential of the environment 6. Measuring the metabolome Future directions * * 1.1 Natural products have been important sources of new leads for the pharmaceutical industry. 1.2 Discovery rates of novel structural classes in decline, the need to bioprospect alternate sources of chemical diversity is evident. 1.3 Microbial genome sequencing projects have revealed the presence of ‘silent’ biosynthetic gene clusters where there is no current detectable. 1.4 Both sources of molecular diversity could encode potentially valuable metabolites. So the ability to measure the entire complement of metabolites within microorganisms that are used as surrogate hosts to express such gene clusters will be crucial to the exploitation of these yet untapped reservoirs of metabolic diversity for future natural product drug discovery. In the past,screening collections of these organisms have been assembled almost randomly,with little previous knowledge of the microbial diversity in the material being sampled,and using techniques of isolation that favored faster growing propagules,such as