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David Cane, PHD

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David Cane

Title: Vernon K. Krieble Professor of Chemistry and Professor of Biochemistry
Department: Chemistry; Biochemistry

david_cane@brown.edu
+1 401 863 3588

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Overview | Research | Grants/Awards | Teaching | Publications

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.

Biography

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.

Research Description

Prof. Cane's major research interests are the elucidation of the enzymology and genetics of biosynthetic pathways.
1) Studies of the genetics and enzymology of polyketide antibiotic biosynthesis are carried out in close collaboration with the group of Prof. Chaitan Khosla of Stanford University. This work includes the study of the antibiotics erythromycin, picromycin, methymycin and tylosin, as well as the polyether antibiotic nanchangmycin (dianemycin, in collaboration with Prof. Zixin Deng of Shanghai Jiaotong University). Major accomplishments in recent years include the development of a sensitive and robust methods to determine the stereochemical specifity of the fundamental polyketide chain building reactions, based on the dissection of modular polyketide synthases into their functional component domains and reconstitution of the activity of the complete modules.
2) Studies of terpenoid synthesizing enzymes have focused in recent years on determination of the structure of these proteins and in the use of various genetic and chemical tools to elucidate the mode of action of these enzymes. One of the great challenges in genomics and proteomics is the identification of the biochemical function of the thousands of uncharacterized gene products that are filling the emerging genome sequence databases. Using an approach that can be called "genome mining" the Cane lab has been expressing and characterizing the component genes of terpenoid biosynthetic gene clusters in Streptomyces species that play an important role in microbial genetics and serve as the sources of majority of known antibiotic natural products. In the course of this work they continue to discover previously unknown enzymes and to identify their mode of action. For example they have now defined the role of all the genes encoding biosynthesis of the antibiotic pentalenolactone and have discovered a completely unanticipated mechanism for the enzymatic formation of geosmin, the ubiquitous microbial metabolite responsible for the characteristic odor of soil and the source of the "off-taste" of water and various foods. Recently Prof. Cane and his coworkers have also uncovered an entirely new pathway for the biosynthesis of a second "off-taste" constituent, methylisoborneol. In collaborative research with Prof. David Christianson of the University of Pennsylvania, they have also continued to determine new terpenoid synthase structures of both native and mutant enzymes, either free or with bound substrates or inhibitors.

Awards

-National Science Foundation, Predoctoral Fellowship, 1966 - 1971

-National Institutes of Health, Postdoctoral Fellowship, 1971 - 1972

-Eli Lilly Grant Award, 1976 - 1978

-Alfred P. Sloan Research Fellow, 1978 - 1982

-National Institutes of Health, Research Career Development Award, 1978 - 1983

-Japan Society for the Promotion of Science Fellow, 1983

-Ernest Guenther Award of the American Chemical Society, 1985

-Fogarty International Center Senior International Fellow, 1989

-Distinguished Visiting Fellow, Christ's College, Cambridge, 1989 - 1990

-John Simon Guggenheim Memorial Foundation Fellow, 1990

-Fulbright Scholar, 1990

-Simonsen Lecturer, Royal Society of Chemistry, 1990 - 1991

-National Institutes of Health, MERIT Award, 1994 - 2004

-Microbial Chemistry Medal of the Kitasato Institute and Kitasato University, 1995

-Fogarty International Center Senior International Fellow, 1999

-Institut Universitaire de France, Fellow, 1999

-A. C. Cope Scholar Award of the American Chemical Society, 2000

-Prelog Lecture and Medal, ETH Zürich, 2002

-Royce Faculty Fellow, 2002-2009

-Fellow of the American Association for the Advancement of Science (AAAS), 2003

-Derek Brewer Visiting Fellow, Emmanuel College, Cambridge, 2004

-Repligen Award in Chemistry of Biological Processes, Division of Biological Chemistry of the American Chemical Society, 2005

-Ph. D. honoris causa University of Kalmar, Sweden, 2007

-Philip J. Bray Award for Teaching Excellence in the Physical Sciences, Brown University, 2008

-Honorary Professor, Wuhan University, 2011

-Alfred Bader Award of the American Chemical Society, 2013

-Fellow of the American Academy of Arts & Sciences

Affiliations

Memberships

-American Chemical Society

-Royal Society of Chemistry

-American Society of Microbiology

-American Society for Biochemistry and Molecular Biology

-American Society of Pharmacognosy

-American Association for the Advancement of Science


Editorial Boards

-Editorial Board, Bioorganic Chemistry, 1983 - 2003

-Editorial Board, Journal of Antibiotics, 1983 -

-Editorial Advisory Board, Chemical Reviews, 1987-1990

-Associate Editor, Journal of Organic Chemistry, 1995 - 2003

-Editorial Advisory Board, Topics in Stereochemistry, 1996 - 2006

-Editorial Board, Current Opinion in Chemical Biology, 1997 -2005

-Faculty of 1000, Contributor, 2000-

-Section Editor, Journal of Antibiotics, 2006 -

-Advisory Board, Wiley Encyclopedia of Chemical Biology, 2006 –


Review Panels/Professional Committees

-NIH Bioorganic and Natural Products Study Section, 1980 - 1984

-ACS Ad Hoc Committee to Review the Journal of Organic Chemistry, 1992 - 1993

-Visiting Committee, Department of Chemistry, Washington State University, 1998

-Alternate Counselor, Biological Chemistry Division, ACS, 1993-1998

-Chair, NIH Scientific Review Group, Centers of Excellence in Chemical

-Methodologies and Library Development, 2002

-NIH SBCB Study Section, 2006

-Chair, External Review Committe, Brandeis University Department of Chemistry, 2006


Consulting

-Consultant, Smith Kline & French Laboratories, 1984 - 1985

-Consultant, American Cyanamid, 1986 -1988

-Myco Pharmaceuticals Lead Discovery Forum, 1993

-Scientific Advisory Board, KOSAN Biosciences, Inc., 1995 - 2006

Funded Research

National Institutes of Health - General Medical Sciences: "The Biosynthesis of Microbial Isoprenoids"; $1,843,318; 4/1/12 - 1/31/16

National Institutes of Health - General Medical Sciences: "Biosynthesis of Microbial Polyketides"; $1,551,878; 9/1/10 - 7/31/14

Teaching Experience

Organic chemistry, biochemistry, enzyme mechanisms, chemical biology

Courses Taught

  • Biochemistry (Mechanistic Enzymology) (Chemistry 1240)
  • Biochemistry - Mechanistic Enzymology (CH0124)
  • Bioorganic Chemistry (CH0123)
  • Organic Chemistry (CH0360)
  • Undergraduate Organic Chemistry (CH0035)
  • Undergraduate Organic Chemistry (CH0036)