title: Biosynthesis of Squalene from Farnesyl Diphosphate in Bacteria: Three Steps Catalyzed by Three Enzymes.
abstract: Squalene (SQ) is an intermediate in the biosynthesis of sterols in eukaryotes and a few bacteria and of hopanoids in bacteria where they promote membrane stability and the formation of lipid rafts in their hosts. The genes for hopanoid biosynthesis are typically located on clusters that consist of four highly conserved genes-hpnC,hpnD,hpnE, andhpnF-for conversion of farnesyl diphosphate (FPP) to hopene or related pentacyclic metabolites. WhilehpnFis known to encode a squalene cyclase, the functions forhpnC,hpnD, andhpnEare not rigorously established. ThehpnC,hpnD, andhpnEgenes fromZymomonas mobilisandRhodopseudomonas palustriswere cloned intoEscherichia coli, a bacterium that does not contain genes homologous tohpnC,hpnD, andhpnE, and their functions were establishedin vitroandin vivo. HpnD catalyzes formation of presqualene diphosphate (PSPP) from two molecules of FPP; HpnC converts PSPP to hydroxysqualene (HSQ); and HpnE, a member of the amine oxidoreductase family, reduces HSQ to SQ. Collectively the reactions catalyzed by these three enzymes constitute a new pathway for biosynthesis of SQ in bacteria.
authors.affiliation: Department of Chemistry, University of Utah, Salt Lake City, Utah 84112, United States.
authors.forename: Jian-Jung
authors.initials: JJ
authors.lastname: Pan
authors.affiliation: Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.
authors.forename: Jose O
authors.initials: JO
authors.lastname: Solbiati
authors.affiliation: Department of Chemistry, University of Utah, Salt Lake City, Utah 84112, United States.
authors.forename: Gurusankar
authors.initials: G
authors.lastname: Ramamoorthy
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, United States.
authors.forename: Brandan S
authors.initials: BS
authors.lastname: Hillerich
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, United States.
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Seidel
authors.affiliation: Department of Microbiology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, United States.
authors.forename: John E
authors.initials: JE
authors.lastname: Cronan
authors.affiliation: Department of Biochemistry, Albert Einstein College of Medicine, Bronx, New York 10461, United States.
authors.forename: Steven C
authors.initials: SC
authors.lastname: Almo
authors.affiliation: Department of Chemistry, University of Utah, Salt Lake City, Utah 84112, United States.
authors.forename: C Dale
authors.initials: CD
authors.lastname: Poulter