title: Two distinct mechanisms for TIM barrel prenyltransferases in bacteria.
abstract: The reactions of two bacterial TIM barrel prenyltransferases (PTs), MoeO5 and PcrB, were explored. MoeO5, the enzyme responsible for the first step in moenomycin biosynthesis, catalyzes the transfer of farnesyl to 3-phosphoglyceric acid (3PG) to give a product containing a cis-allylic double bond. We show that this reaction involves isomerization to a nerolidyl pyrophosphate intermediate followed by bond rotation prior to attack by the nucleophile. This mechanism is unprecedented for a prenyltransferase that catalyzes an intermolecular coupling. We also show that PcrB transfers geranyl and geranylgeranyl groups to glycerol-1-phosphate (G1P), making it the first known bacterial enzyme to use G1P as a substrate. Unlike MoeO5, PcrB catalyzes prenyl transfer without isomerization to give products that retain the trans-allylic bond of the prenyl donors. The TIM barrel family of PTs is unique in including enzymes that catalyze prenyl transfer by distinctly different reaction mechanisms.
authors.affiliation: Department of Chemistry and Chemical Biology, Harvard University, 12 Oxford Street, Cambridge, Massachusetts 02139, United States.
authors.forename: Emma H
authors.initials: EH
authors.lastname: Doud
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Perlstein
authors.forename: Manuel
authors.initials: M
authors.lastname: Wolpert
authors.forename: David E
authors.initials: DE
authors.lastname: Cane
authors.forename: Suzanne
authors.initials: S
authors.lastname: Walker
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000737:chemistry; D000595:Amino Acid Sequence; D001419:Bacteria / Q000201:enzymology*; D004122:Dimethylallyltranstransferase / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid; D014305:Triose-Phosphate Isomerase / Q000378:metabolism*
chemical_list: D019883:Alkyl and Aryl Transferases; D004122:Dimethylallyltranstransferase; C083737:phosphoglycerol geranylgeranyltransferase; D014305:Triose-Phosphate Isomerase