个人简介

David E. Cane was born in New York in 1944. After undergraduate study at Harvard, he received his Ph. D. in 1971 from Harvard University for research in organic synthesis carried out under the direction of Prof. E. J. Corey. During this period he developed an interest in the origins of natural products that led him to pursue postdoctoral study in natural products biosynthesis and bioorganic chemistry with Prof. Duilio Arigoni at the Eidgenössiche Technische Hochschule in Zürich. In 1973, he joined the faculty of Brown University where he is now Vernon K. Krieble Professor of Chemistry and Professor of Biochemistry. His research interests include the chemistry, enzymology and molecular genetics of natural products biosynthesis. This research has led to the identification, purification, and characterization of a variety of new enzymes that catalyze the conversion of the universal acyclic precursor, farnesyl diphosphate, to cyclic sesquiterpenes. Studies on these enzymes have established many key details of this fascinating cyclization process. In addition, cloning, over-expression, and site-directed mutagenesis of terpenoid synthase genes has provided large quantities of protein for further mechanistic and structural studies, and resulted in the elucidation of several crystal structures of a terpene synthase, the latter work carried out in collaboration with Prof. David W. Christianson of the University of Pennsylvania. In work on macrolide antibiotics, carried out in close collaboration with Prof. Chaitan Khosla of Stanford University, a combination of synthetic, enzymological, and molecular genetic approaches is being used to clarify the intricate sequence of events that is required to convert the simple building blocks such as acetate and propionate to complex macrolides such as the broad spectrum antibiotic erythromycin A and picromycin. In other recent work, Prof. Cane and his collaborators have investigated the enzymology and mechanism of formation of vitamin B6 and have established the role of two key enzymes in the formation of the characteristic pyridoxine ring. Prof. Cane has been a Fellow of the Japan Society for the Promotion of Science (1983) and a John Simon Guggenheim Memorial Foundation Fellow (1990), and has twice held Senior International Fellowships (1990, 1999) from the Fogarty International Center of the National Institutes of Health. In addition, he has received a number of awards, including the Ernest Guenther Award (1985), the Cope Scholar Award (2000), the Repligen Award (2005), and the Alfred Bader Award (2013) of the American Chemical Society, the Simonsen Lecture of the Royal Society of Chemistry (1990-91), the Kitasato Medal in Microbial Chemistry (1995), the Prelog Medal of the Eidgenössische Technische Hochschule, Zürich, and a Ph. D. (honoris causa) from the University of Kalmar, Sweden. He is a Fellow of the American Association of the Advancement of Science and of the American Academy of Arts & Sciences. In addition to over 305 scientific publications, in 2003 he co-edited a book of his father's World War II Letters published by Fordham University Press.

研究领域

antibiotics/biosynthesis/mechanistic enzymology/natural products/polyketides protein structure/terpenoids

The main focus of Professor Cane's research has been to establish the mechanism of formation of a wide variety of naturally occurring substances of diverse biological origins. These metabolites include antibiotics, toxins, plant defense substances, essential oils, and vitamins. Over the last several years his research group has concentrated on the mechanistic enzymology and molecular genetics of two broad areas, terpenoid metabolism and polyketide antibiotic biosynthesis.

近期论文

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Liansuo Zu, Meimei Xu, Michael W. Lodewyk, David E. Cane, Reuben J. Peters, and Dean J. Tantillo, "Effect of Isotopically Sensitive Branching on Product Distribution for Pentalenene Synthase – Support for a Mechanism Predicted by Quantum Chemistry," J. Am. Chem. Soc. 134, 11369-11371. (PMID: 22738258; PMCID: PMC3402234 [Available on 2013/7/18]) Colin J. B. Harvey, Joseph D. Puglisi, Vijay S. Pande, David E. Cane, and Chaitan Khosla, "Precursor Directed Biosynthesis of an Orthogonally Functional Erythromycin Analog: Selectivity in the Ribosome Macrolide Binding Pocket," J. Am. Chem. Soc.134, 12259-12265. (PMID: 22741553; PMCID: PMC3405186 [Available on 2013/7/25]) Satoshi Yuzawa, Shiven Kapur, David E. Cane, and Chaitan Khosla, "Role of a Conserved Arginine Residue in Linkers between the Ketosynthase and Acyltransferase Domains of Multimodular Polyketide Synthases," Biochemistry 51, 3708-3710 (2012).(PMID: 22509729; PMCID: PMC3348408 [Available on 2013/5/8]) David E. Cane, "Favouring the Unfavoured," Nature, 483, 285-286 (2012). (PMID: 22422260). Shiven Kapur, Brian Lowry, Satoshi Yuzawa, Sanketha Kenthirapalan, Alice Y. Chen, David E. Cane, and Chaitan Khosla, "Reprogramming a Module of the 6-Deoxyerythronolide B Synthase for Iterative Chain Elongation," Proc. Natl. Acad. Sci. USA, 109, 4110-4115 (2012). (PMID: 22371562; PMCID: PMC3306671 [Available on 2012/9/13]). Xun Guo, Tiangang Liu, Zixin Deng, and David E. Cane, "Essential Role of the Donor Acyl Carrier Protein in Stereoselective Chain Translocation to a Fully Reducing Module of the Nanchangmycin Polyketide Synthase," Biochemistry 51, 879-887 (2012). (PMID: 22229794). David E. Cane and Haruo Ikeda, "Exploration and Mining of the Bacterial Terpenome," Acc. Chem. Res. 45, 463-472 (2012) (PMID: 22039990) Fong T. Wong, Xi Jin, Irimpan I. Mathews, David E. Cane, Chaitan Khosla, "Structure and Mechanism of the trans-Acting Acyltransferase from the Disorazole Synthase," Biochemistry 50, 6539-6548 (2011) (PMID: 21707057; PMCID: PMC3144309). Wayne K. W. Chou, Haruo Ikeda, and David E. Cane, "Cloning and characterization of Pfl_1841, a 2-methylenebornane synthase in Pseudomonas fluorescens PfO-1," Tetrahedron 67, 6627-6632 (2011) (PMID: 21804650). Louise K. Charkoudian, Corey W. Liu, Stefania Capone, David E. Cane, Antonio Togni, Dieter Seebach, and Chaitan Khosla, "Probing the Interactions of an Acyl Carrier Protein Domain from the 6-Deoxyerythonolide B Synthase," Protein Sci. 20, 1244-1255 (2011) (PMID: 21563224). Dongqing Zhu, Myung-Ji Seo, Haruo Ikeda, and David E. Cane, "Genome Mining in Streptomyces. Discovery of an Unprecedented P450-Catalyzed Oxidative Rearrangement That is the Final Step in the Biosynthesis of Pentalenolactone," J. Am. Chem. Soc. 133, 2128-2131 (2011) (PMID: 21284395; PMCID: PMC3041837). Myung-Ji Seo, Dongqing Zhu, Saori Endo, Haruo Ikeda, and David E. Cane, "Genome Mining in Streptomyces. Elucidation of the Role of Baeyer-Villiger Monooxygenases and Non-Heme Iron-Dependent Dehydrogenase/Oxygenases in the Final Steps of the Biosynthesis of Pentalenolactone and Neopentalenolactone," Biochemistry 50, 1739-1754 (2011 (PMID: 21250661). Emma H. Doud, Deborah L. Perlstein, Manuel Wolpert, David E. Cane⊥, Suzanne Walker, "Two distinct mechanisms for TIM barrel prenyltransferases in bacteria," J. Am. Chem. Soc. 133, 1270-1273 (2011) (PMID: 21214173). Yunfeng Hu, Wayne K. W. Chou, Russell Hopson, and David E. Cane, "Genome Mining in Streptomyces clavuligerus. Expression and Biochemical Characterization of Two Cryptic Sesquiterpene Cyclases, (-)-δ-Cadinene Synthase and (+)-T-Muurolol Synthase" Chem. Biol. 18, 32-37 (2011) (PMID: 21276937; PMCID: PMC3034312). Ho Young Lee, Colin J. B. Harvey, David E. Cane, and Chaitan Khosla, "Improved Precursor Directed Biosynthesis in E. coli via Directed Evolution," J. Antibiot. 64, 59-64 (2011) (PMID: 21081955; PMCID: PMC3030684 ). Steven Giglio, Wayne K. W. Chou, Haruo Ikeda, David E. Cane D.E. and Paul T. Monis, "Biosynthesis of 2-methylisoborneol in cyanobacteria," Environ. Sci. Tech. 45, 992-998 (2011) (PMID: 21174459). Satoshi Takamatsu, Lian-Hua Xu, Shinya Fushinobu, Hirofumi Shoun, Mamoru Komatsu, David E. Cane, and Haruo Ikeda, "Pentalenic acid is a shunt metabolite in pentalenolactone family metabolite biosynthesis: Hydroxylation of 1-deoxypentalenic acid mediated by CYP105D7 (SAV_7469) of Streptomyces avermitilis," J. Antibiot. 64, 65-71 (2011) (PMID: 21081950; PMCID: PMC3030646). Chiara R. Valenzano, Young-Ok You, Ashish Garg, Adrian Keatinge-Clay, Chaitan Khosla, and David E. Cane, "Stereospecificity of the Dehydratase Domain of the Erythromycin Polyketide Synthase," J. Am. Chem. Soc. 132, 14697-14699 (2010) (PMID: 20925342; PMCID: PMC2959128). Xun Guo, Tiangang Liu, Chiara R. Valenzano, Zixin Deng, and David E. Cane, "Mechanism and Stereospecificity of a Fully Saturating Polyketide Synthase Module: Nanchangmycin Synthase Module 2 and Its Dehydratase Domain," J. Am. Chem. Soc. 132, 14694-14696 (2010) (PMID: 20925339; PMCID: PMC2959152). David E. Cane, "Programming of erythromycin biosynthesis by a modular polyketide synthase," J. Biol. Chem. 285, 27517-27523 (2010 (PMID: 20522551; PMCID: PMC2934617)). Shiven Kapur, Alice Y. Chen, Satoshi Yuzawa, David E. Cane, Chaitan Khosla, "Molecular Recognition between Ketosynthase and Acyl Carrier Protein Domains of the 6-Deoxyerythronolide B Synthase," Proc. Natl. Acad. Sci. U.S.A. 107, 22066-22071 (2010) (PMID: 21127271; PMCID: PMC3009775). Wayne K. W. Chou, Immacolata Fanizza, Takuma Uchiyama, Mamoru Komatsu, Haruo Ikeda, and David E. Cane, "Genome mining in Streptomyces avermitilis: Cloning and characterization of SAV_76, the synthase for a new sesquiterpene, avermitilol," J. Am. Chem. Soc. 132, 8850-8851 (2010) (PMID: 20536237; PMCID: PMC2904616). Satoshi Takamatsu, Xin Lin, Ayako Nara, Mamoru Komatsu, David E. Cane, and Haruo Ikeda, "Activation of a silent sesquiterpenoid biosynthetic pathway in Streptomyces avermitilis controlling epi-isozizaene and albaflavenone biosynthesis and isolation of a new oxidized epi-isozizaene metabolite," Microb. Biotech. 4, 184-191 (2011) (PMID: 21342464). Mamoru Komatsu, Takuma Uchiyama, Satoshi Omura, David E. Cane, and Haruo Ikeda, "Genome-minimized Streptomyces host for the heterologous expression of secondary metabolism," Proc. Natl. Acad. Sci. U.S.A 107, 2646-2651 (2010) (PMID: 20133795; PMCID: PMC2823899). Fong T. Wong, Alice Y. Chen, David E. Cane, and Chaitan Khosla, "Protein-Protein Recognition between Acyltransferases and Acyl Carrier Proteins in Multimodular Polyketide Synthases," Biochemistry 49, 95-102 (2010). Julie A. Aaron, Xin Lin, David E. Cane and David W. Christianson, "Structure of Epi-Isozizaene Synthase from Streptomyces coelicolor A3(2), a Platform for New Terpenoid Cyclization Templates" Biochemistry 49, 1787-1797 (2010).