title: Moonlighting Metals: Insights into Regulation of Cyclization Pathways in Fungal Δ(6) -Protoilludene Sesquiterpene Synthases.
abstract: Fungal 1,11 cyclizing sesquiterpene synthases are product specific under typical reaction conditions. However, in vivo expression of certain Δ(6)-protoilludene synthases results in dual 1,11 and 1,10 cyclization. To determine the factors regulating this mechanistic variation, in-depth in vitro characterization of Δ(6)-protoilludene synthases was conducted. Divalent metal ions determine cyclization specificity and this product variability. Promiscuity in metal binding is mediated by secondary metal-binding sites away from the conserved D(D/E)XX(D/E) motif in sesquiterpene synthases. Phylogenetic analysis revealed a divergent evolution of Basidiomycota trans-humulyl cation producing sesquiterpene synthases, results that indicate a wider diversity in function than previously predicted. This study provides key insights into the function and evolution of 1,11 cyclizing fungal sesquiterpene synthases.
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, 1479 Gortner Avenue, St. Paul, MN, 55108, USA.
authors.forename: Maureen B
authors.initials: MB
authors.lastname: Quin
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, 1479 Gortner Avenue, St. Paul, MN, 55108, USA.
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Michel
authors.affiliation: Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, 1479 Gortner Avenue, St. Paul, MN, 55108, USA. schmi232@umn.edu.
authors.forename: Claudia
authors.initials: C
authors.lastname: Schmidt-Dannert
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000737:chemistry / Q000378:metabolism*; D001487:Basidiomycota / Q000201:enzymology*; D003500:Cyclization; D008670:Metals / Q000737:chemistry / Q000378:metabolism*; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes / Q000737:chemistry / Q000378:metabolism*
chemical_list: D008670:Metals; D000081223:Polycyclic Sesquiterpenes; D012717:Sesquiterpenes; C506221:protoilludane; D019883:Alkyl and Aryl Transferases; C108877:terpene synthase
keywords: GC/MS; biosynthesis; kinetics; natural products