S188: Sesquiterpenoid biosynthetic diversity in higher fungi

Thursday, July 28, 2011: 4:00 PM
Bayside A, 4th fl (Sheraton New Orleans)
Claudia Schmidt-Dannert, Dept. Biochemistry, Molecular Biology & Biophysics, University of Minnesota, St. Paul, MN
Higher fungi (basidiomycetes) represent a rich source for the discovery of novel, bioactive sesquiterpene pathways. Only very little is known about the biosynthesis of this major class of natural products made by basidiomycetes. We therefore have recently begun to shift of focus in terpenoid biosynthesis towards this class of organism. Our studies show that basidiomycetes synthesize a variety of different sesquiterpenoid structures. We have identified and characterized six different sesquiterpenoid synthases along with tailoring enzymes in Coprinus cinerea [1]. Functional and mutagenesis studies provided new insights into the catalytic promiscuity [2] as well as selectivity [3] of fungal sesquiterpene synthases. More recently, we have initiated genome-wide surveys of sesquiterpene synthase diversity in basidiomycetes. We find that this class of enzymes has undergone substantial gene duplication in basidiomycetes. Cloning and functional characterization of some of these enzymes provides us with new insights into the structural diversity of sesquiterpenoids produced by these fungi.

[1] S. Agger, F. Lopez-Gallego and C. Schmidt-Dannert (2009) Diversity of sesquiterpene synthases in the basidiomycete Coprinus cinereus. Mol. Microbiol. 72:1181-95

[2] F. Lopez-Gallego, S. Agger, D. Abate-Pella, M. D. Distefano and C. Schmidt-Dannert (2010) Sesquiterpene synthases Cop4 and Cop6 from Coprinus cinereus: Catalytic promiscuity and cyclization of farnesyl pyrophosphate geometrical isomers. Chembiochem 11:1093-106

[3]  F. López-Gallego, G. Wawrzyn and C. Schmidt-Dannert (2010) Enzyme selectivity of fungal sesquiterpene synthases: the role of the active site H-1a loop in catalysis. Appl Environ Microbiol. 76:7723-33