title: Chimeras of two isoprenoid synthases catalyze all four coupling reactions in isoprenoid biosynthesis.
abstract: The carbon skeletons of over 55,000 naturally occurring isoprenoid compounds are constructed from four fundamental coupling reactions: chain elongation, cyclopropanation, branching, and cyclobutanation. Enzymes that catalyze chain elongation and cyclopropanation are well studied, whereas those that catalyze branching and cyclobutanation are unknown. We have catalyzed the four reactions with chimeric proteins generated by replacing segments of a chain-elongation enzyme with corresponding sequences from a cyclopropanation enzyme. Stereochemical and mechanistic considerations suggest that the four coupling enzymes could have evolved from a common ancestor through relatively small changes in the catalytic site.
authors.affiliation: Department of Chemistry, University of Utah, 315 South 1400 East, Room 2020, Salt Lake City, UT 84112, USA.
authors.forename: Hirekodathakallu V
authors.initials: HV
authors.lastname: Thulasiram
authors.forename: Hans K
authors.initials: HK
authors.lastname: Erickson
authors.forename: C Dale
authors.initials: CD
authors.lastname: Poulter
mesh_terms: D000595:Amino Acid Sequence; D019306:Artemisia / Q000201:enzymology; D002384:Catalysis; D020134:Catalytic Domain; D011723:Chrysanthemum cinerariifolium / Q000201:enzymology; D003521:Cyclopropanes / Q000737:chemistry; D019143:Evolution, Molecular; D051228:Geranyltranstransferase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D015394:Molecular Structure; D016297:Mutagenesis, Site-Directed; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D013237:Stereoisomerism; D013729:Terpenes / Q000737:chemistry / Q000378:metabolism*
chemical_list: D003521:Cyclopropanes; D011993:Recombinant Fusion Proteins; D013729:Terpenes; C030797:cyclopropane; C518835:chrysanthemyl diphosphate synthase, Chrysanthemum; D051228:Geranyltranstransferase