Natural products produced by many plants, bacteria and fungi as secondary metabolites have been the major drug source for pharmaceutical industry for the last several decades. Enediyne natural products discovered in 1980s are unique member among natural product family with potent DNA cleavage activity. A typical enediyne natural product is structurally characterized by a highly unsaturated enediyne core containing two acetylenic groups conjugated to a double bond in nine- or ten- membered carbocycle. Thus the enediyne natural products are conveniently categorized into two subfamilies, nine-membered enediynes and ten-membered enediynes.several examples of nine-membered enediynes (C-1027 from Streptomyces globisporus and neocarzinostatin from Streptomyces macromomyceticus) and ten-membered enediynes (calicheamicin from Micromonospora echinospora and esperamicin from Actinomadura verrucosopora.
Although total synthesis of almost all enediyne natural products has been achieved by organic synthesis, the blue print of their biosynthesis in cells is still not quite clear to us. Before discovery and sequencing of enediyne gene clusters, researchers speculated biosynthesis pathways of enediyne natural products by biomimetic synthesis and feeding of isotope labeled starting material to enediyne producing bacteria strains.
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