B.A. Chemistry (1984) Bethel College
Ph.D. Chemistry (1994) Harvard University
Recombinant biosynthetic approaches to natural product biosynthesis. Directed evolution and DNA shuffling to generate new oxidosqualene cyclases. Metabolic engineering to produce terpenes.
Email: matsuda@rice.edu
Phone: (713) 348-6158
Office: George R. Brown Hall, W300E
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Seiichi Matsuda
E. Dell Butcher Professor of Chemistry and Professor of Biochemistry & Cell Biology
Research Statement
Terpenoids are compounds derived from isopentenyl pyrophosphate. They are the most numerous and structurally diverse group of natural products, with 22,000 members displaying more than 300 ring systems. Terpenoids that play crucial roles in vertebrates include the retinoids, the geranylgeranyl and farnesyl protein anchors, the coenzymes Q, vitamins A, D, and E, cholesterol, and the steroid hormones. Terpenoid hormones and pheromones are equally important in invertebrates. Plants control growth and development using regulatory terpenes including  the gibberellins, the brassinosteroids, and abscissic acid. Many plants synthesize defense terpenoids that interfere with biological processes in potential herbivores. Some of these compounds are medicinally useful, such as taxol (anticancer), ginkgolide (which delays onset and progression of Alzheimer's disease), and artemisinin (antimalarial). We are cloning and characterizing genes encoding terpene cyclases and terpene oxidases, which catalyze terpene biosynthesis. We engineer microbial metabolic pathways by heterologously expressing these genes. The resultant strains produce natural products, many of which are difficult to obtain by existing methodology. Terpene synthases catalyze spectacular reactions, such as the conversion of epoxysqualene to cycloartenol. We are modifying terpene biosynthetic genes to produce catalysts that make novel natural products. In collaboration with Bonnie Bartel in this department, we are studying the function of terpenoids in the plant Arabidopsis thaliana.
Selected Publications
Shan, H., Wilson, W.K., Phillips, D.R., Bartel, B., and Matsuda, S.P.T. "Trinorlupeol: a major nonsterol triterpenoid in Arabidopsis." Organic Letters, 10 (2008): 1897-1900.
J. M. Rasbery, H. Shan, R. J. LeClair, M. Norman, S. P. T. Matsuda, and B. Bartel "Arabidopsis thaliana Squalene Epoxidase 1 is Essential for Root and Seed Development." J. Biol. Chem., 282 (2007): 17002-17013.
M. D. Kolesnikova, W. K. Wilson, William; D. A. Lynch, A. C. Obermeyer, S. P. T. Matsuda "Arabidopsis camelliol C synthase evolved from enzymes that make pentacycles." Org. Lett., 9 (2007): 5223 -5226.
S. Lodeiro, Q. Xiong, W. K. Wilson, M. D. Kolesnikova, C. S. Onak, and S. P. T. Matsuda "An oxidosqualene cyclase makes numerous products by diverse mechanisms: a challenge to prevailing concepts of triterpene biosynthesis." J. Am. Chem. Soc., 129 (2007): 11213-11222.
M. D. Kolesnikova, A. C. Obermeyer, W. K. Wilson, D. A. Lynch, Q. Xiong, and S. P. T. Matsuda "The stereochemistry of water addition in triterpene synthesis: the structure of arabidiol." Org. Lett., 9 (2007): 2183-2186.
S. Lodeiro, W. K. Wilson, H. Shan, and S. P. T. Matsuda "A putative precursor of isomalabaricane triterpenoids from lanosterol synthase mutants." Org. Lett., 8 (2006): 439-442.
Q. Xiong, W. K. Wilson, and S. P. T. Matsuda "An Arabidopsis oxidosqualene cyclase catalyzes iridal skeleton formation via Grob fragmentation." Angew. Chem., 45 (2006): 1285-1288.
D. R. Phillips, J. M. Rasbery, B. Bartel, and S. P. T. Matsuda "Biosynthetic diversity in plant triterpene cyclization." Curr. Opin. Plant Biol., 9 (2006): 305-314.
M. D. Kolesnikova, Q. Xiong, S. Lodeiro, L. Hua, and S. P. T. Matsuda "Lanosterol biosynthesis in plants." Arch. Biochem. Biophys., 447 (2006): 87-95.
S. P. T. Matsuda, W. K. Wilson, and Q. Xiong "Mechanistic insights into triterpene synthesis from quantum mechanical calculations. Detection of systematic errors in B3LYP cyclization energies." Org. Biomol. Chem. (2006): 530-543.
Presentations
"DNA-based approaches to Natural Products Chemistry." Baylor University Department of Chemistry, Waco, TX. (October 24, 2008)
"Robert A. Welch Lecture: On the Origins of Triterpenoid Skeletal Diversity." Texas Lutheran University, Seguin, TX. (February 8, 2008)
"Robert A. Welch Lecture: On the Origins of Triterpenoid Skeletal Diversity." Texas A&M University at Kingsville, Kingsville, TX. (October 17, 2007)
"On the Origins of Triterpenoid Skeletal Diversity." 13th European Congress on Biotechnology, Barcelona, Spain. (September 17, 2007)
Theses
Carrie McNeil, Ph.D. "Metabolic engineering approaches to biosynthesize terpenoids in Saccharomyces cerevisiae." (2008).(Thesis or Dissertation Director)
Mariya Kolesnikova, Ph.D. "Investigation of the Triterpene Biosynthesis in Arabidopsis thaliana." (2008).(Thesis or Dissertation Director)
Awards
Matt Suffness Award, American Society of Pharmacognosy. (2003).
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