Enediyne antitumor antibiotics

Liu, W. and Shen, B. (2000) Genes for production of the enediyne antitumor antibiotic C-1027 in Streptomyces globisporus are clustered with the cagA gene that encodes the C-1027 apoprotein. Antimicrobial Agents and Chemotherapy, 44, 382. 

Zhang, J., Van Lanen, S.G., Ju, J. et al. (2008) A phosphopantetheinylatingpolyketide synthase producing a linear polyene to initiate enediyne antitumor antibiotic biosynthesis. Proceedings of the National Academy of Sciences of the United States of America, 105, 1460. 

Before the advent of enediyne antitumor antibiotics, there had been few examples of carbon radicals believed to mediate DNA cleavage. The simplest of all, the methyl radical has been shown to effect DNA cleavage under enzymatic as well as chemical conditions [24]. Oxidation of methylhydrazine by horseradish peroxidase or ferricyanide (Fig. 5) gave high yields of methyl radicals, which were shown to cleave DNA by purine ring alkylation. 

Van Lanen SG, Dorrestein PC, Christenson SD, Liu W, Ju J, Kelleher NL, Shen B (2005) Biosynthesis of the (3-Amino Acid Moiety of the Enediyne Antitumor Antibiotic C-1027 Featuring (3-Amino Acyl-S-carrier Protein Intermediates. J Am Chem Soc 127 11594... 

Lin S, Van Lanen SG, Shen B (2007) Regiospecific Chlorination of (S)-P-Tyrosyl-S-Carrier Protein Catalyzed by SgcC3 in the Biosynthesis of the Enediyne Antitumor Antibiotic C-1027. J Am Chem Soc 129 12432... 

Murrell JM, Liu W, Shen B (2004) Biochemical characterization of the SgcAl a-D-gluco-pyranosyl-l-phosphate thymidylyltransferase from the enediyne antitumor antibiotic C-1027 biosynthetic pathway and overexpression of sgcAl in Streptomyces globisporus to improve C-1027 production. J Nat Prod 67 206-213... 

Doyle, T.W. and Borders, D. B., Enediyne antitumor antibiotics, in Enediyne Antibiotics as Antitumor Agents, Borders, D. B. and Doyle, T. W., Eds., Marcel Dekker, New York, 1995, chap. 1. 

In 1974, Dickson and Fraser reviewed the already substantial area of cobalt-alkyne complexes.1 Since then the number of examples and applications of this class of organometallic compounds, especially dinuclear complexes, has increased enormously. This review will present the chemistry of polynuclear cobalt-alkyne complexes, with emphasis on the more recent developments. Although there have been many exciting fundamental discoveries, this is a maturing area of research that is finding many important applications in organic synthesis,2 such as the use of [Co2(jU-alkyne)(CO)6] complexes in the synthesis of enediyne antitumor antibiotics.3-4... 

Biggins JB, Onwueme KC, Thorson JS. Resistance to enediyne antitumor antibiotics by CalC self-sacrifice. Science 2003 301(5639) 1537-1541. 

Christenson SD, Liu W, Toney, MD, Shen B. A novel 4-methylideneimidazole-5-one-containing tyrosine aminomutase in enediyne antitumor antibiotic C-1027 biosynthesis. J. Am. Chem. 57. Soc. 2003 125 6062-6063. 

Vuljanic, T, Kihlberg, J, Somfai, P, Diastereoselective synthesis of methyl a-kedarosaminide, a carbohydrate moiety of the enediyne antitumor antibiotic kedaricidin chromophore. Tetrahedron Lett., 35, 6937-6940, 1994. 

Oku, N. Matsunaga, S. Fusetani, N. Shishijimicins A-C, novel enediyne antitumor antibiotics from the Ascidian Didemnum proliferum. J. Am. Chem. Soc. 2003, 125, 2044-2045. 

Audrain, H. Skrydstrup, T. Ulibarri, G. Riche, C. Chiaroni, A. Grierson, D.S. Application and mechanistic studies of the [2,3]-Wittig rearrangement an approach to the bicyclic core structure of the enediyne antitumor antibiotics calicheamicin y/ and esperamicin-Ai. Tetrahedron 1994, 50, 1469-1502. 

Xu J, Zhen Y, Goldberg IH. C1027 chromophore, a potent new enediyne antitumor antibiotic, induces sequence-specific double-strand DNA cleavage. Biochemistry. 1994 33 5947-5954. 

Liu W, Christenson SD, Standage S, Shen B (2002) Biosynthesis of the enediyne antitumor antibiotic C-1027. Science 297 1170-1173... 

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