A phosphopantetheinylating polyketide synthase producing a linear polyene to initiate enediyne antitumor antibiotic biosynthesis

作者: J. Zhang , S. G. Van Lanen , J. Ju , W. Liu , P. C. Dorrestein

DOI: 10.1073/PNAS.0711625105

关键词:

摘要: The enediynes, unified by their unique molecular architecture and mode of action, represent some the most potent anticancer drugs ever discovered. biosynthesis enediyne core has been predicted to be initiated a polyketide synthase (PKS) that is distinct from all known PKSs. Characterization PKS involved in C-1027 (SgcE) neocarzinostatin (NcsE) now revealed (i) PKSs contain central acyl carrier protein domain C-terminal phosphopantetheinyl transferase domain; (ii) are functional heterologous hosts, coexpression with an thioesterase gene produces first isolable compound, 1,3,5,7,9,11,13-pentadecaheptaene, biosynthesis; (iii) findings for SgcE NcsE likely shared among nine-membered thereby supporting common mechanism initiate biosynthesis.

参考文章(50)
Otto Meth-Cohn, 香爾 中西, Barton, Derek, Sir, Comprehensive natural products chemistry Elsevier. ,(1999)
Fabienne Fichtlscherer, Christian Wellein, Maria Mittag, Eckhart Schweizer, A novel function of yeast fatty acid synthase European Journal of Biochemistry. ,vol. 267, pp. 2666- 2671 ,(2000) , 10.1046/J.1432-1327.2000.01282.X
Sueharu Horinouchi, Nobutaka Funa, Yasuo Ohnishi, Isao Fujii, Masaaki Shibuya, Yutaka Ebizuka, A new pathway for polyketide synthesis in microorganisms Nature. ,vol. 400, pp. 897- 899 ,(1999) , 10.1038/23748
Wen Liu, Steven D Christenson, Scott Standage, Ben Shen, Biosynthesis of the Enediyne Antitumor Antibiotic C-1027 Science. ,vol. 297, pp. 1170- 1173 ,(2002) , 10.1126/SCIENCE.1072110
Gregory L. Challis, Stuart W. Haynes, Non-linear enzymatic logic in natural product modular mega-synthases and -synthetases. Current Opinion in Drug Discovery & Development. ,vol. 10, pp. 203- 218 ,(2007)
D. W. Udwary, L. Zeigler, R. N. Asolkar, V. Singan, A. Lapidus, W. Fenical, P. R. Jensen, B. S. Moore, Genome sequencing reveals complex secondary metabolome in the marine actinomycete Salinispora tropica Proceedings of the National Academy of Sciences of the United States of America. ,vol. 104, pp. 10376- 10381 ,(2007) , 10.1073/PNAS.0700962104
Michael B Austin, Tamao Saito, Marianne E Bowman, Stephen Haydock, Atsushi Kato, Bradley S Moore, Robert R Kay, Joseph P Noel, Biosynthesis of Dictyostelium discoideum differentiation-inducing factor by a hybrid type I fatty acid–type III polyketide synthase Nature Chemical Biology. ,vol. 2, pp. 494- 502 ,(2006) , 10.1038/NCHEMBIO811
Julian Davies, Hao Wang, Terry Taylor, Kaoru Warabi, Xin-Hui Huang, Raymond J. Andersen, Uncialamycin, a new enediyne antibiotic. Organic Letters. ,vol. 7, pp. 5233- 5236 ,(2005) , 10.1021/OL052081F
Pieter C. Dorrestein, Jonathan Blackhall, Paul D. Straight, Michael A. Fischbach, Sylvie Garneau-Tsodikova, Daniel J. Edwards, Shaun McLaughlin, Myat Lin, William H. Gerwick, Roberto Kolter, Christopher T. Walsh, Neil L. Kelleher, Activity Screening of Carrier Domains within Nonribosomal Peptide Synthetases Using Complex Substrate Mixtures and Large Molecule Mass Spectrometry Biochemistry. ,vol. 45, pp. 1537- 1546 ,(2006) , 10.1021/BI052333K