David E. Cane - Recent Publications

Recent Publications

Xin Lin and David E. Cane, “Biosynthesis of theSesquiterpene Antibiotic Albaflavenone in Streptomyces coelicolor. Mechanism and Stereochemistry of the Enzymatic Formation of Epi-isozizaene,” J. Am. Chem. Soc. 131, 6332-6333 (2009).

Tiangang Liu, David E. Cane, Zixin Deng, “Polyethers,” Meth. Enzymology 459, 187-214 (2009).

Chaitan Khosla, Shiven Kapur, and David E. Cane, “Revisiting the Modularity of Modular Polyketide Synthases,” Curr. Opin. Chem. Biol. 13, 135-143 (2009).

Cristina Pinedo, Chieh-Mei Wang, Jean-Marc Pradier, Bérengère Dalmais, Mathias Choquer, Pascal Le Pêcheur, Guillaume Morgant, Isidro G. Collado, David E. Cane, Muriel Viaud, “The Sesquiterpene Synthase from the Botrydial Biosynthetic Gene Cluster of the Phytopathogen Botrytis cinerea,” ACS Chem. Biol. 3, 791-801 (2008).

Steven Giglio, Jiaoyang Jiang, Christopher P Saint, David Cane, and Paul T Monis, “Isolation and Characterization of the Gene Associated with Geosmin Production in Cyanobacteria,” Env. Sci. Technol. 42, 8027–8032 (2008).

Roselyne Castonguay, Chiara R. Valenzano, Alice Y. Chen, Adrian Keatinge-Clay, Chaitan Khosla, and David E. Cane, “Stereospecificity of Ketoreductase Domains 1 and 2 of the Tylactone Modular Polyketide Synthase,” J. Am. Chem. Soc. 130, 11598-11599 (2008).

Chieh-Mei Wang and David E. Cane, “Biochemistry and Molecular Genetics of the Biosynthesis of the Earthy Odorant Methylisoborneol in Streptomyces coelicolor,” J. Am. Chem. Soc.130, 8908-8909 (2008).

Tiangang Liu, Xin Lin, Xiufen Zhou, Zixin Deng, and David E. Cane, “Mechanism of Thioesterase-Catalyzed Chain Release in the Biosynthesis of the Polyether Antibiotic Nanchangmycin,” Chem. Biol.15, 449-458 (2008).

Ekaterina Y. Shishova, Fanglei Yu, David J. Miller, Juan A. Faraldos, Yuxin Zhao, Robert M. Coates, Rudolf K. Allemann, David E. Cane, and David W. Christianson, “X-ray Crystallographic Studies of Substrate Binding to Aristolochene Synthase Suggest a Metal Binding Sequence for Catalysis,” J. Biol. Chem. 283, 15431-15439 (2008).

Shiven Kapur, Andrew Worthington, Yinyan Tang, David E. Cane, Michael D. Burkart, and Chaitan Khosla, “Mechanism based protein cross-linking of domains from the 6-deoxyerythronolide B synthase,” Bioorg. Med. Chem. Lett. 18, 3034-3038 (2008).

Bin Zhao, Xin Lin, Li Lei, David C. Lamb, Steven L. Kelly, Michael R. Waterman, and David E. Cane, “Biosynthesis of the Sesquiterpene Antibiotic Albaflavenone in Streptomyces Coelicolor A3(2),” J. Biol. Chem. 283, 8183-8189 (2008).

Thorben Nawrath,Jeroen S. Dickschat,Rolf Müller,Jiaoyang Jiang, David E. Cane, and Stefan Schulz, "Identification of (8S,9S,10S)-8,10-dimethyl-1-octalin, a key intermediate in the biosynthesis of geosmin in bacteria," J. Am. Chem. Soc. 130, 428-429 (2008).

Jiaoyang Jiang and David E. Cane, “Geosmin Biosynthesis. Mechanism of the Fragmentation–Rearrangement in the Conversion of Germacradienol to Geosmin,” J. Am. Chem. Soc. 130, 428-429 (2008).

L. Sangeetha Vedula, David E. Cane, and David W. Christianson, “Structural and Mechanistic Analysis of Trichodiene Synthase using Site-Directed Mutagenesis: Probing the Catalytic Function of Tyrosine-295 and the Asparagine-225/Serine-229/Glutamate-233–Mg2+Motif,” Arch. Biochem. Biophys., 469, 184-194 (2008).

Zheng You, Satoshi Omura, Haruo Ikeda, David E. Cane, and Gerwald Jogl, “Crystal Structure of the Non-heme Iron Dioxygenase PtlH in Pentalenolactone Biosynthesis,” J. Biol. Chem. 282, 36552-36560 (2007).

Roselyne Castonguay, Weiguo He, Alice Y. Chen, Chaitan Khosla, and David E. Cane, “Stereospecificity of Ketoreductase Domains of the 6-Deoxyerythronolide B Synthase,” J. Am. Chem. Soc.129, 13758-13769 (2007).

Viktor Y. Alekseyev, Corey W. Liu, David E. Cane, Joseph D. Puglisi, and Chaitan Khosla, “Solution Structure and Proposed Domain-domain Recognition Interface of an Acyl Carrier Protein Domain from a Modular Polyketide Synthase,” Protein. Sci. 16, 2093-2107 (2007).

L. Sangeetha Vedula, Yuxin Zhao, Robert M. Coates, Tanetoshi Koyama, David E. Cane, and David W. Christianson, “Exploring Biosynthetic Diversity with Trichodiene Synthase,” Arch. Biochem. Biophys. 466, 260-266 (2007).

Jiaoyang Jiang, Xiaofei He, and David E. Cane, “Biosynthesis of the earthy odorant geosmin by a bifunctional Streptomyces coelicolor enzyme,” Nat. Chem. Biol. 11, 711-715 (2007).

Yinyan Tang, Chu-Young Kim, Alice Y. Chen, David E. Cane, and Chaitan Khosla, “Structural and Mechanistic Analysis of Protein Interactions in Module 3 of the 6-Deoxyerythronolide B Synthase,” Chem. Biol. 14, 931-943 (2007).

Alice Y. Chen, David E. Cane, and Chaitan Khosla, “Structure-Based Dissociation of a Type I Polyketide Synthase Module” Chem. Biol. 14, 784-792 (2007).

Chaitan Khosla, Yinyan Tang, Alice Y. Chen, Nathan A. Schnarr, and David E. Cane, “Structure and Mechanism of the 6-Deoxyerythronolide B Synthase,” Ann. Rev. Biochem. 76, 195-221 (2007).

Ekaterina Y. Shishova, Luigi Di Constanzo, David E. Cane, and David W. Christianson, “Crystal Structure of Aristolochene Synthase from Aspergillus terreus and the Evolution of Templates for the Cyclization of Farnesyl Diphosphate,” Biochemistry 46, 1941-1951 (2007).

Zheng You, Satoshi Omura, Haruo Ikeda, and David E. Cane, “Pentalenolactone biosynthesis. Molecular cloning and assignment of biochemical function to PtlF, a short-chain dehydrogenase from Streptomyces avermitilis, and identification of a new biosynthetic intermediate,” Arch. Biochem. Biophys.459, 233-240 (2007).

Tiangang Liu, Delin You, Chiara Valenzano, Yuhui Sun, Jialiang Li, Qin Yu, Xiufen Zhou, David E. Cane, Zixin Deng, “Identification of NanE as a Unique Thioesterase for Polyether Chain Release in Nanchangmycin Biosynthesis,” Chem. Biol. 13, 945-955 (2006).

Richard Quaderer,Satoshi Omura, Haruo Ikeda, and David E. Cane, “Pentalenolactone Biosynthesis. Molecular Cloning and Assignment of Biochemical Function to PtlI, a Cytochrome P450 of Streptomyces avermitilis,” J. Am. Chem. Soc.128, 13036-13037 (2006).

David E. Cane, Xiaofei He, Seiji Kobayashi, Satoshi Omura, and Haruo Ikeda, “Geosmin Biosynthesis in Streptomyces avermitilis. Molecular Cloning, Expression, and Mechanistic Study of the Germacradienol/Geosmin Synthase,” J. Antibiotics, 59, 471-479 (2006).

Jiaoyang Jiang, Xiaofei He, and David E. Cane, “Geosmin Biosynthesis. Streptomyces coelicolor Germacradienol/Germacrene D Synthase Converts Farnesyl Diphosphate to Geosmin,” J. Am. Chem. Soc. 128, 8128-8129 (2006).

Xin Lin, Russell Hopson, and David E. Cane, “Genome Mining in Streptomyces coelicolor. Molecular Cloning and Characterization of a New Sesquiterpene Synthase,” J. Am. Chem. Soc. 128, 6022-6023 (2006).

Zheng You, Satoshi Omura, Haruo Ikeda, and David E. Cane “Pentalenolactone Biosynthesis. Molecular Cloning and Assignment of Biochemical Function to PtlH, a Non-Heme Iron Dioxygenase of Streptomyces avermitilis,” J. Am. Chem. Soc. 128, 6566-6567 (2006).

Charles N. Tetzlaff, Zheng You, David E. Cane, Satoshi Takamatsu, Satoshi Omura and Haruo Ikeda, “A Gene Cluster for Pentalenolactone Biosynthesis in Streptomyces avermitilis,” Biochemistry 45, 6179-6186 (2006).

Yinyan Tang, Chu-Young, Kim, Irimpan I. Matthews, Alice Y. Chen, David E. Cane, and Chaitan Khosla, “The 2.7 Å Crystal Structure of a 194-kDa Homodimeric Fragment of the 6-Deoxyerythronolide B Synthase,” Proc. Natl. Acad. Sci. USA, 103, 11124-11129 (2006).

Alice Y. Chen, Nathan A. Schnarr, Chu-Young Kim, David E. Cane, and Chaitan Khosla “Extender Unit and Acyl Carrier Protein Specificity of Ketosynthase Domains of the 6-Deoxyerythronolide B Synthase,” J. Am. Chem. Soc. 128, 3067-3074 (2006).

David E. Cane, “Brushes with Sage,” Arch. Biochem. Biophys. 448, 117-122 (2006).

Sarah Picaud, Per Mercke, Xiaofei, Olov Sterner, Maria Brodelius, David Cane, and Peter E. Brodelius,“ Amorpha-4,11-diene synthase. Mechanism and stereochemistry of the enzymatic cyclization of farnesyl diphosphate,” Arch. Biochem. Biophys. 448, 150-155 (2006).

Weiguo He, Jiaquan Wu, Chaitan Khosla, and David E. Cane “Macrolactonization to 10-Deoxymethynolide Catalyzed by the Recombinant Thioesterase of the Picromycin/Methymycin Polyketide Synthase” Bioorganic Med. Chem. Lett. 16, 391-394 (2006).

David A. Moffet, Chaitan Khosla, and David E. Cane, “Modular Polyketide Synthases: Investigating Intermodular Communication Using 6-Deoxyerythronolide B Synthase Module 2” Bioorganic Med. Chem. Lett. 16, 213-216 (2006).

Jiaquan Wu, Toby J. Zaleski, Chaitan Khosla, and David E. Cane, “ Polyketide Double Bond Biosynthesis. Mechanistic Analysis of the Dehydratase-Containing Module of the Picromycin/Methymycin Polyketide Synthase,” J. Am. Chem. Soc. 127, 17393-17404 (2005).

Jiaquan Wu, Weiguo He, Chaitan Khosla, and David E. Cane, “Chain-Elongation, Macrolactonization, and Hydrolysis of Natural and Reduced Hexaketide Substrates by the Picromycin/Methymycin Polyketide Synthase,” Angew. Chemie Intl. Ed.44, 7557-7560 (2005).

L. Sangeetha Vedula, David E. Cane, and David W. Christianson, “Role of Arginine-304 in the Diphosphate-Triggered Active Site Closure Mechanism of Trichodiene Synthase,” Biochemistry 44, 12719-12727 (2005).

Nathan A. Schnarr, Alice Y. Chen, David E. Cane, and Chaitan Khosla, “Analysis of Covalently Bound Polyketide Intermediates on the 6-Deoxyerythronolide B synthase by Tandem Proteolysis - Mass Spectrometry,” Biochemistry 44 11836-11842 (2005).

L. Sangeetha Vedula, Michael J. Rynkiewicz, Hyung-Jung Pyun, Robert M. Coates, David E. Cane, and David W. Christianson, “Molecular Recognition of the Substrate Diphosphate Group Governs Product Diversity in Trichodiene Synthase Mutants,” Biochemistry 44, 6153-6163 (2005).

Jiaquan Wu, Kenji Kinoshita, Chaitan Khosla, and David E. Cane, “Biochemical Analysis of the Substrate Specificity of the b-Ketoacyl-Acyl Carrier Protein Synthase Domain of Module 2 of the Erythromycin Polyketide Synthase,” Biochemistry 43, 16301-16310 (2004).

Chu-Young Kim, Viktor Y. Alekseyev, Alice Y. Chen, Yinyan Tang, David E. Cane, and Chaitan Khosla, “Reconstituting Modular Activity from Separated Domains of 6-deoxyerythronolide B Synthase,” Biochemistry 43, 13892-13898 (2004).

Stéphane B. Richard, Antonietta M. Lillo, Charles N. Tetzlaff, Marianne E. Bowman, Joseph P. Noel, and David E. Cane, “Kinetic analysis of E. coli 2-C-methyl-D-erythritol-4-phosphate cytidyltransferase (YgbP), wild-type and mutants, reveals roles of active site amino acids,” Biochemistry 43, 12189-12197 (2004).

David E. Cane, “Back to Basics: Assigning Biochemical Function in the Post-Genomic Era,” Chemistry & Biology, 11, 741-743 (2004).

Brunella Felicetti and David E. Cane, “Aristolochene Synthase. Mechanistic Analysis of Active Site Residues by Site-Directed Mutagenesis,” J. Am. Chem. Soc. 126, 7212-7221 (2004).

Jerel Banks and David E. Cane, “Biosynthesis of Vitamin B6: Direct Identification of the Product of the PdxA-Catalyzed Oxidation of 4-Hydroxy-L-threonine-4-phosphate Using Electrospray Ionization Mass Spectrometry,” Bioorg. Med. Chem. Lett. 14, 1633-1636 (2004).

Xiaofei He and David E. Cane, “Mechanism and Stereochemistry of the Germacradienol/Germacrene D Synthase of Streptomyces coelicolor A3(2)” J. Am. Chem. Soc. 126, 2678-2679 (2004).

Kenji Watanabe, Clay C. C. Wang, Christopher N. Boddy, David E. Cane, and Chaitan Khosla, “Understanding Substrate Specificity of Polyketide Synthase Modules by Generating Hybrid Multimodular Synthases,” J. Biol. Chem. 278, 42020-42026 (2003).

Kenji Kinoshita, Chaitan Khosla, and David E. Cane, “Precursor-Directed Biosynthesis: Stereospecificity for Branched-Chain Diketides of the b-Ketoacyl-ACP Synthase Domain 2 of 6-Deoxyerythronolide B Synthase,” Helv. Chim. Acta 86, 3889-3905 (2003).

Pawan Kumar, Andrew T. Koppisch, David E. Cane and Chaitan Khosla, “Enhancing the Modularity of the Modular Polyketide Synthases: Transacylation in Modular Polyketide Synthases Catalyzed by Malonyl-CoA:ACP Transacylase,” J. Am. Chem. Soc. 125, 14307-14312 (2003).

Kenji Kinoshita, Blaine A. Pfeifer, Chaitan Khosla, and David E. Cane, “Precursor-Directed Polyketide Biosynthesis in E. coli,” Bioorg. Med. Chem. Lett. 13, 3701-3704 (2003).

J. Sivaraman, Yunge Li, Jerel Banks, David E. Cane, Miroslaw Cygler, and Allan Matte, “Crystal Structure of E. coli PdxA, an Enzyme Involved in the Pyridoxal Phosphate Biosynthesis Pathway,” J. Biol. Chem. 278, 43682-43690 (2003).

Lawrence Cane, "Fighting Fascism in Europe. The World War II Letters of an American Veteran of the Spanish Civil War," David E. Cane, Judy Barrett Litoff, and David C. Smith, eds, Fordham University Press, New York, 2003.

Yifeng Yin, Hongxiang Lu, Chaitan Khosla, and David E. Cane, "Expression and Kinetic Analysis of the Substrate Specificity of Modules 5 and 6 of the Picromycin/Methymycin Polyketide Synthase," J. Am. Chem. Soc. 125, 5671-5676 (2003).

Pawan Kumar, Qing Li, David E. Cane, and Chaitan Khosla, "Intermodular Communication in Modular Polyketide Synthases: Structural and Mutational Analysis of Linker Mediated Protein-Protein Recognition," J. Am. Chem. Soc. 125, 4097-4102 (2003).

David E. Cane, "Mechanism and Structure of Biosynthetic Enzymes. The Biosynthesis of Vitamin B6," Prelog Lecture, ETH, Laboratorium fur Organische Chemie, November 11, 2002, Chimia 74, 71-74 (2003).

Marcus Hans, Andreas Hornung, Agnieszka Dziarnowski, David E. Cane and Chaitan Khosla, O`Mechanistic Analysis of Acyl Transferase Domain Exchange in Polyketide Synthase Modules, J. Am. Chem. Soc. 123, 5822-5823 (2001).

David E. Cane and Rory M. Watt, "Functional Expression and Mechanistic Characterization of a Germacradienol Synthase from Streptomyces coelicolor Implicated in Geosmin Biosynthesis," Proc. Natl. Acad. Sci. USA,100, 1547-1551 (2003) .

Grace F. Liou, Janice Lau, David E. Cane, and Chaitan Khosla, "Quantitative Analysis of Loading and Extender Acyltransferases of Modular Polyketide Synthases," Biochemistry, 41, 200-207 (2002).

Antonietta M. Lillo, Charles N. Tetzlaff, Felix J. Sangari, David E. Cane, "Functional Expression and Characterization of EryA, the Erythritol Kinase of Brucella abortus and enzymatic synthesis of L-erythritol-4-phosphate," Bioorg. Med. Chem. Lett. 13, 737-739 (2003).

Joanne I Yeh, Shoucheng Du, Ehmke Pohl, and David E. Cane, "Multistate Binding in Pyridoxine 5'-Phosphate Synthase: 1.95 ? Crystal Structure in Complex with 1-deoxy-D-xylulose phosphate," Biochemistry 41, 11649-11657 (2002).

Shiou-Chuan Tsai, Hongxiang Lu, David E. Cane, Chaitan Khosla, and Robert M. Stroud, "Insights into Channel Architecture and Substrate Specificity from Crystal Structures of Two Macrocycle Forming Thioesterases of Modular Polyketide Synthases," Biochemistry 41, 12598-12606 (2002).

Hongxiang Lu, Shiou-Chuan Tsai, Chaitan Khosla, and David E. Cane, "Expression, Site-Directed Mutagenesis, and Steady State Kinetic Analysis of the Terminal Thioesterase Domain of the Methymycin/Picromycin Polyketide Synthase," Biochemistry 41, 12590-12597 (2002).

Myriam Seemann, Guangzhi Zhai, Jan-Willem de Kraker, Chiana M. Paschall, David W. Christianson, and David E. Cane, "Pentalenene Synthase. Analysis of Active Site Residues by Site-Directed Mutagenesis," J. Am. Chem. Soc.124, 7681-7689 (2002).

Stephane B. Richard, Jean-Luc Ferrer, Marianne E. Bowman, Antonietta M. Lillo, Charles N. Tetzlaff, David E. Cane, and Joseph P. Noel, "Structure and Mechanism of 2-C-Methyl-D-Erythritol 2,4-Cyclodiphosphate Synthase. Active Site Architecture Supporting Formation of a Cyclodiphosphate-Containing Isoprenoid Precursor," J. Biol. Chem. 277, 8667-8672 (2002)

Nicholas Wu, David E. Cane, and Chaitan Khosla, "Quantitative Analysis of the Relative Contributions of Donor Acyl Carrier Proteins, Acceptor Ketosynthases, and Linker Regions to Intermodular Transfer of Intermediates in Hybrid Polyketide Synthases," Biochemistry 41, 5056-5066 (2002).

Michael J. Rynkiewicz, David E. Cane, and David W. Christianson, "X-ray crystal structures of D100E trichodiene synthase and its diphosphate complex reveal basis for terpene product diversity," Biochemistry 41, 1732-1741 ( 2002).

David E. Cane, Fumitaka Kudo, Kenji Kinoshita, and Chaitan Khosla, "Precursor-Directed Biosynthesis. Kinetic Analysis Reveals the Biochemical Basis of the Remarkable Selectivity of the Erythromycin Polyketide Synthase Towards Unsaturated Triketides," Chem. Biol. 9, 131-142 (2002).

Michael J. Rynkiewicz, David E. Cane, and David W. Christianson, "Structure of trichodiene synthase from Fusarium sporotrichioides provides mechanistic inferences on the terpene cyclization cascade," Proc. Natl. Acad. Sci. USA 98, 13543-13548 (2001).

Shiou-chuan Tsai, Jolanta Krucinski, Larry Miercke, Rajesh Gokhale, Julian Chen, Paul Foster, David E. Cane, Chaitan Khosla, and Robert Stroud, "Crystal Structure of the Terminal Thioesterase Domain of the Erythromycin Polyketide Synthase: Versatility from a Unique Substrate Channel," Proc. Natl. Acad. Sci. USA 98, 14808-14813 (2001).

Huawei Chen, Sarah O'Connor, David E. Cane, Christopher T. Walsh, "Epothilone Biosynthesis: Assembly of the Methythiazolylcarboxy Starter Unit on the EpoB Subunit," Chem. Biol. 8, 899-912 (2001).

Nicholas Wu, Stuart Y. Tsuji, David E. Cane, and Chaitan Khosla, "Assessing the Balance between Protein-Protein Interactions and Enzyme-Substrate Interactions in the Channeling of Intermediates Between Polyketide Synthase Modules," J. Am. Chem. Soc., 123, 6465-6474 (2001).

Nicola Pohl, Marcus Hans, Hwan Young Lee, Yu Sam Kim, David E. Cane, Chaitan Khosla, "Remarkably Broad Substrate Tolerance of Malonyl-CoA Synthetase, and Enzyme Capable of Intracellular Synthesis of Polyketide Precursors," J. Am. Chem. Soc. 123, 5822-5823 (2001).

Stephane B. Richard, Marianne E. Bowman, Witek Kwiatkowski, Ilgu Kang, Cathy Chow, David E. Cane, and Joseph P. Noel, "Structure of 4-diphosphocytidyl-2-C-methylerythritol synthase involved in mevalonate-independent isoprenoid biosynthesis," Nature Struct. Biol., 8, 641-648 (2001).

Blaine A. Pfeifer, Suzanne J. Admiraal, Hugo Gramajo, David E. Cane and Chaitan Khosla, "Biosynthesis of Complex Polyketides in a Metabolically Engineered Strain of Escherichia coli," Science 291, 1790-1792 (2001).

Kenji Kinoshita, Paul G Williard, Chaitan Khosla, and David E. Cane, "PrecursorDirected Biosynthesis of 16-Membered Macrolides by the Erythromycin Polyketide Synthase," J. Am. Chem. Soc. 123, 2495-2502 (2001).

David E. Cane, Cathy Chow, Antonietta Lillo, and Ilgu Kang, "Molecular Cloning, Expression and Characterization of the First Three Genes in the Mevalonate-Independent Isoprenoid Pathway in Streptomyces coelicolor," Bioorg. Med. Chem. 9, 1467-1477 (2001).

Stuart Tsuji, David. E. Cane, and Chaitan Khosla, "Selective Protein-Protein Interactions Direct Channeling of Intermediates Between Polyketide Synthase Modules," Biochemistry, 40, 2326-2331 (2001).

Yifeng Yin, Rajesh Ghokale, Chaitan Khosla, and David E. Cane, "Erythromycin Biosynthesis. The 4-pro-S hydride of NADPH is Utilized for Ketoreduction by Both Module 5 and Module 6 of the 6-Deoxyerythronolide B Synthase," Bioorg. Med. Chem. Lett. 11, 1477-1479 (2001).

Janice Lau, David E. Cane, and Chaitan Khosla, "Substrate Specificity of the Loading Didomain of the Erythromycin Polyketide Synthase," Biochemistry 39, 10514-10520 (2000).

David E. Cane, Shoucheng Du, and Ian D. Spenser, "Biosynthesis of Vitamin B6: Origin of the Oxygen Atoms of Pyridoxol Phosphate," J. Am. Chem. Soc. 122, 4213-4214 (2000).

Nicholas Wu, Fumitaka Kudo, David E. Cane, and Chaitan Khosla, "Analysis of the Molecular Recognition Features of Individual Modules Derived from the Erythromycin Polyketide Synthase," J. Am. Chem. Soc. 122, 4847-4852 (2000).

David E. Cane, "Biosynthesis Meets Bioinformatics," Science, 287, 818-819 (2000).

David E. Cane and Ilgu Kang, "Aristolochene Synthase. Purification, Molecular Cloning, High-Level Expression in Escherichia coli, and Characterization of the Aspergillus terreus Cyclase," Arch. Biochem. Biophys. 376, 354-364 (2000).

Jonathan M. Caruthers, Ilgu Kang, Michael J. Rynkiewicz, David E. Cane, and David W. Christianson, "Crystal Structure Determination of Aristolochene Synthase from the Blue Cheese Mold, Penicillium roqueforti,", J. Biol. Chem. 275, 25533-25539 (2000).

David E. Cane and Ning Ke, "Epicubenol Synthase. Origin Of The Oxygen Atom Of A Bacterial Sesquiterpene Alcohol," Bioorg. Med. Chem. Lett. 10, 105-107 (2000).

David E. Cane and Christopher T. Walsh, "Crosstalk: The Parallel and Convergent Universes of Polyketide Synthases and Nonribosomal Peptide Synthetases," Chemistry & Biology 6, R319-R325 (1999).

David E. Cane, Shoucheng Du, J. Kenneth Robinson, Yuju Hsiung, and Ian D. Spenser, "Biosynthesis of Vitamin B6. Enzymatic Conversion of 1-Deoxy-D-xylulose-5-phosphate to Pyridoxol Phosphate," J. Am. Chem. Soc. 121, 7722-7723 (1999).

David E. Cane and Todd E. Bowser, "Trichodiene Synthase. Mechanism-Based Inhibition Of A Sesquiterpene Cyclase," Bioorg. Med. Chem. Lett. 9, 1127-1132 (1999).

Rajesh S. Gokhale, Stuart Y. Tsuji, David E. Cane, and Chaitan Khosla, "Dissecting and exploiting Intermodular Communication in Polyketide Synthases," Science, 284, 482-485 (1999).

Daniel Hunziker, Nicholas Wu, Kenji Kinoshita, David E. Cane, and Chaitan Khosla, "Precursor Directed Biosynthesis of Novel 6-Deoxyerythronolide B Analogs Containing Non-natural Oxygen Substituents and Reactive Functionalities," Tetrahedron Lett. 40, 635-638 (1999).

Myriam Seemann, Guangzhi Zhai, Kazuo Umezawa and David Cane, "Pentalenene Synthase. Histidine-309 is Not Required for Catalytic Activity," J. Am. Chem. Soc. 121, 591-592 (1999).

Rajesh S. Gokhale, Daniel Hunziker, David E. Cane, and Chaitan Khosla, "Mechanism and Specificity of the Terminal Thioesterase Domain from the Erythromycin Polyketide Synthase," Chemistry & Biology, 6, 117-125 (1999).

Chaitan Khosla, Rajesh S. Gokhale, John R. Jacobsen, and David E. Cane, "Tolerance and Specificity of Polyketide Synthases," Ann. Rev. Biochem. 68, 219-253 (1999).

Janice Lau, Hong Fu, David E. Cane, and Chaitan Khosla, "Dissecting the Role of Acyltransferase Domains of Modular Polyketide Synthases in the Choice and Stereochemical Fate of Extender Units," Biochemistry 38, 1643-1651 (1999).

Nicola L. Pohl, Rajesh S. Gokhale, David E. Cane, and Chaitan Khosla, "Synthesis and Incorporation of an N-Acetyl Cysteamine Analog of Methylmalonyl-CoA by a Modular Polyketide Synthase," J. Am. Chem. Soc. 120, 11206-11207 (1998).

David E. Cane, "Sesquiterpene Biosynthesis. Cyclization Mechanisms," in "Isoprenoids, Including Carotenoids and Steroids," ed., David E. Cane, "Comprehensive Natural Products Chemistry," Vol. 2, Elsevier, London,1998.

"Isoprenoids, Including Carotenoids and Steroids," ed., David E. Cane, "Comprehensive Natural Products Chemistry," Vol. 2, Elsevier, London, 1998.

Edmund I. Graziani, David E. Cane, Melanie C. Betlach, James T. Kealey, and Robert McDaniel, "Macrolide Biosynthesis: A Single Cytochrome P450, PicK, is Responsible for the Hydroxylations that Generate Methymycin, Neomethymycin, and Picromycin in Streptomyces venezuelae,"Bioorg. Med. Chem. Letters, 8, 3117-3120 (1998).

David E. Cane, Christopher T. Walsh, and Chaitan Khosla, "Harnessing the Biogenetic Code: Combinations, Permutations, and Mutations," Science, 282, 63-68 (1998).

John R. Jacobsen, David E. Cane, and Chaitan Khosla, "Dissecting the Evolutionary Relationship Between 14-Membered and 16-Membered Macrolides," J. Am. Chem. Soc., 120, 9096-9097 (1998).

John R. Jacobsen, Adrian Keatinge-Clay, David E. Cane, and Chaitan Khosla, "Precursor-Directed Biosynthesis of 12-Ethyl Erythromycin," Bioorg. Med. Chem. 6, 1171-1177 (1998).

David E. Cane and Edmund I. Graziani, "Methymycin Biosynthesis. Isolation of P450 Monooxygenase Activity in a Cell-Free System from Streptomyces venezuelae," J. Am. Chem. Soc., 120, 2682-2683 (1998).

David E. Cane, Yuju Hsiung, Julie A. Cornish, J. Kenneth Robinson, and Ian D. Spenser, "Biosynthesis of Vitamin B6: The Oxidation of 4-Hydroxy-L-threonine 4-Phosphate by PdxA," J. Am .Chem. Soc. 120, 1936-1937 (1998).

John R. Jacobsen, David E. Cane, and Chaitan Khosla, "Spontaneous Decarboxylative Priming of a Downstream Module in 6-Deoxyerythronolide B Synthase," Biochemistry 37, 4928-4934 (1998).

Rajesh S. Gokhale, Janice Lau, David E. Cane, and Chaitan Khosla, "Functional Orientation of the Acyl Transferase Domain in a Module of the Erythromycin Polyketide Synthase," Biochemistry 37, 2524-2528 (1998).

Michael McPherson, Chaitan Khosla, and David E. Cane, "Erythromycin Biosynthesis: The beta-Ketoreductase Domains Catalyze the Stereospecific Transfer of the 4-pro-S Hydride of NADPH," J. Am. Chem. Soc. 120, 3267-3268 (1998).

"Alcohol Stereochemistry in Polyketide Backbones is Controlled by the b-Ketoreductase Domains of Modular Polyketide Synthases," J. Am. Chem. Soc. 120, 2478-2479 (1998).

David E. Cane, "Polyketide and Nonribosomal Polypeptide Synthesis, From Collie to Coli" Chem. Reviews 97, 2463-2464 (1997).

David E. Cane, Guest Editor, Chem. Reviews, "Polyketide and Nonribosomal Polypeptide Synthesis," 97 (7) (1997).

Jo-Anne Chuck, Michael McPherson, Hai Huang, John R. Jacobsen, Chaitan Khosla, and David E. Cane, "Molecular recognition of diketide substrates by a beta-ketoacyl-ACP synthase domain within a bimodular polyketide synthase," Chem. Biol. 4, 757-766 (1997).

Camilla M. Kao, Mike McPherson, Robert N. McDaniel, Hong Fu, David E. Cane, and Chaitan Khosla, "Gain of Function Mutagenesis of the Erythromycin Polyketide Synthase. II. Engineered Biosynthesis of an Eight-Membered Tetraketide Lactone," J. Am. Chem. Soc. 119, 11339-11340 (1997).

Charles A. Lesburg, Guangzhi Zhai, David E. Cane, and David W. Christianson, "Crystal Structure of Pentalenene Synthase: Mechanistic Insights on Terpenoid Cyclization Reactions in Biology," Science, 277, 1820-1824 (1997).

John R. Jacobsen, C. Richard Hutchinson, David E. Cane, and Chaitan Khosla, "Precursor Directed Biosynthesis of Novel Erythromycin Analogs by an Engineered Polyketide Synthase," Science, 277, 367-369 (1997).

Robert McDaniel, Camilla M. Kao, Hong Fu, Peter Hevezi, Claes Gustafsson, Mary Betlach, Gary Ashley, David E. Cane, and Chaitan Khosla, "Gain-of-Function Mutagenesis of the Erythromycin Polyketide Synthase," J. Am. Chem. Soc., 119, 4309-4310 (1997).

David E. Cane, Hsien-Tai Chiu, Po-Huang Liang, and Karen S. Anderson, "A Pre-Steady State Kinetic Analysis of the Trichodiene Synthase Reaction Pathway," Biochemistry, 36 , 8332 -8339 (1997).

Rembert Pieper, Rajesh S. Gokhale, Guanglin Luo, David E. Cane, and Chaitan Khosla, "Purification and Characterization of Bimodular and Trimodular Derivatives of the Erythromycin Polyketide Synthase," Biochemistry, 36, 1846-1851 (1997).

Naohiro Tsukamoto, Jo-Anne Chuck, Guanglin Luo, Camilla M. Kao, Chaitan Khosla, and David E. Cane, "6-Deoxyerythronolide B synthase 1 is specifically acylated by a diketide intermediate at the [[beta]]-ketoacyl-ACP synthase domain of module 2," Biochemistry 35, 15244-15248 (1996).

Camilla M. Kao, Rembert Pieper, David E. Cane, and Chaitan Khosla, "Evidence for Two Catalytically Independent Clusters of Active Sites in a Functional Modular Polyketide Synthase," Biochemistry 35, 12363-12368 (1996).

David E. Cane, Qun Xue, and Brian C. Fitzsimons, "Trichodiene Synthase. Probing the Role of the Highly Conserved Aspartate-Rich Region by Site-Directed Mutagenesis," Biochemistry, 35, 12369-12376 (1996).

David E. Cane, Qun Xue, and James E. Van Epp, "Enzymatic Formation of Isochamigrene, a Novel Sesquiterpene, by Alteration of the Aspartate-Rich Region of Trichodiene Synthase," J. Am. Chem. Soc. 118, 8499-8500 (1996).

David E. Cane and Youla S. Tsantrizos, "Aristolochene Synthase. Elucidation of the Cryptic Germacrene A Synthase Activity Using the Anomalous Substrate Dihydrofarnesyl Diphosphate," J. Am. Chem. Soc. 118, 10037-10040 (1996).

David Bedford, John R. Jacobsen, Guanglin Luo, David E. Cane, and Chaitan Khosla, "A Functional Chimeric Modular Polyketide Synthase Generated via Domain Replacement," Chem. Biol., 3, 827-831 (1996).

Alison Hill, David E. Cane, Christopher D. Mau, and Charles West, "High Level Expression of Ricinus communis Casbene Synthase in Escherichia coli and Characterization of the Recombinant Enzyme," Arch. Biochem. Biophys. 336, 283-289 (1996).

Naohiro Tsukamoto, Jo-Anne Chuck, Guanglin Luo, David E. Cane, and Chaitan Khosla, "6-Deoxyerythronolide B synthase 1 is specifically acylated by a diketide intermediate at the beta-ketoacyl-ACP synthse domain of module 2," Biochemistry 35, 15244-15248 (1996).

Rembert Pieper, Camilla Kao, Chaitan Khosla, Guanglin Luo and David E. Cane, "Specificity and Versatility in Erythromycin Biosynthesis," Chem. Soc. Rev. 25, 297-302 (1996).

Camilla M. Kao, Guanglin Luo, Leonard Katz, David E. Cane, and Chaitan Khosla, "Engineered Biosynthesis of Structurally Diverse Tetraketides by a Trimodular Polyketide Synthase, " J. Am. Chem. Soc. 118, 9184-9185 (1996).

Guanglin Luo, Rembert Pieper, Angela Rosa, Chaitan Khosla, and David E. Cane, "Erythromycin Biosynthesis: Exploiting the Catalytic Versatility of the Modular Polyketide Synthase," Bioorganic Med. Chem. 74, 995-999 (1996).

Rembert Pieper, Susanne Ebert-Khosla, David Cane, and Chaitan Khosla, "Erythromycin Biosynthesis:Kinetic Studies On A Fully Active Modular Polyketide Synthase Using Natural and Unnatural Substrates," Biochemistry, 35, 2054-2060 (1996).

David E. Cane and Qun Xue, "Trichodiene Synthase. Enzymatic Formation of Multiple Sesquiterpenes by Alteration of the Cyclase Active Site," J. Am. Chem. Soc. , 118, 1563-1564 (1996).