Biomedical subjects
Publications and source records attributed to Tsion Bililign.
Two recent papers in Science reported the X-ray structures of the large, organizationally distinct animal and fungal fatty acid synthases at 5 A. These new structural insights have unexpected implications for enzyme function for the other "iterative" and "assembly line" megasynthases.
The focus of this review is to highlight the structure, bioactivity and biosynthesis of naturally occurring aryl-C-glycosides. General synthetic methods and their relevance to proposed biochemical mechanisms for the aryl-C-glycoside bond formation are also presented.
The biosynthetic gene cluster for the pluramycin-type antitumor antibiotic hedamycin has been cloned from Streptomyces griseoruber. Sequence analysis of the 45.6 kb region revealed a variety of unique features such as a fabH homolog (KSIII), an acyltransferase (AT) gene, a set of type I polyketide synthase (PKS) genes, and two putative C-glycosyltransferase genes. As the first report of the cloning of the biosynthetic gene cluster for the pluramycin antibiotics, this work suggests that the biosynthesis of pluramycins utilize an iterative type I PKS system for the generation of a novel starter unit that subsequently primes the type II PKS system. It also implicates the involvement of a second catalytic ketosynthase (KSIII) to regulate this unusual priming step. Gene disruption is used to confirm the importance of both type I and II PKS genes for the biosynthesis of hedamycin.
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