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Big effects from small changes: Possible ways to explore nature's chemical diversity
Bode, HB; Bethe, B; Hofs, R; Zeeck, A
Source PublicationCHEMBIOCHEM
AbstractFungi or bacteria that produce secondary metabolites often have the potential to bring up various compounds from a single strain. The molecular basis for this well-known observation was observation was confirmed in the last few years by several sequencing projects of different microorganisms. Besides well-known examples about induction of a selected biosynthesis (for example, by high- or low-phosphate cultivation media), no overview about the potential in this field for finding natural products was given. We have investigated the systematic alteration of easily accessible cultivation parameters (for example, media composition, aeration, culture vessel, addition of enzyme inhibitors) in order to increase the number of secondary metabolites available from one microbial source. We termed this way of revealing nature's chemical diversity the 'OSMAC (One Strain - Many Compounds) approach' and by using it we were able to isolate up to 20 different metabolites in yields up to 2.6 g L-1 from a single organism. These compounds cover nearly all major natural product families, and in some cases the high production titer opens new possibilities for semisynthetic methods to enhance even more the chemical diversity of selected compounds. The OSMAC approach offers a good alternative to industrial high-throughput screening that focuses on the active principle in a distance bioassay. In consequence, the detection of additional compounds that might be of interest as lead structures in further bioassays is impossible and clearly demonstrates the deficiency of the industrial procedure. Furthermore, our approach seems to be a useful tool to detect those metabolites that are postulated to be the final products of an amazing number of typical secondary metabolite genes clusters identified in microorganisms. If one assumes a (more or less) defined reservoir of genetic possibilities for several biosynthetic pathways in one strain that is used for a highly flexible production of secondary metabolites depending on the environment, the OSMAC approach might give more insight into the role of secondary metabolism in the microbial community or during the evolution of life itself.
KeywordMyxobacterium Stigmatella-aurantiaca Precursor-directed Biosynthesis Sphaeropsidales Sp F-24'707 Alpha-l-rhamnopyranosides Soil Dna Libraries Secondary Metabolites Polyketide Synthase Aspergillus-melleus Drug Discovery Cladospirone Bisepoxide
Document Type期刊论文
Recommended Citation
GB/T 7714
Bode, HB,Bethe, B,Hofs, R,et al. Big effects from small changes: Possible ways to explore nature's chemical diversity[J]. CHEMBIOCHEM,2002,3(7):619-627.
APA Bode, HB,Bethe, B,Hofs, R,&Zeeck, A.(2002).Big effects from small changes: Possible ways to explore nature's chemical diversity.CHEMBIOCHEM,3(7),619-627.
MLA Bode, HB,et al."Big effects from small changes: Possible ways to explore nature's chemical diversity".CHEMBIOCHEM 3.7(2002):619-627.
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