title: The Arabidopsis thaliana FPP synthase isozymes have overlapping and specific functions in isoprenoid biosynthesis, and complete loss of FPP synthase activity causes early developmental arrest.
abstract: Farnesyl diphosphate (FPP) synthase (FPS) catalyses the synthesis of FPP, the major substrate used by cytosolic and mitochondrial branches of the isoprenoid pathway. Arabidopsis contains two farnesyl diphosphate synthase genes, FPS1 and FPS2, that encode isozymes FPS1L (mitochondrial), FPS1S and FPS2 (both cytosolic). Here we show that simultaneous knockout of both FPS genes is lethal for Arabidopsis, and embryo development is arrested at the pre-globular stage, demonstrating that FPP-derived isoprenoid metabolism is essential. In addition, lack of FPS enzyme activity severely impairs male genetic transmission. In contrast, no major developmental and metabolic defects were observed in fps1 and fps2 single knockout mutants, demonstrating the redundancy of the genes. The levels of sterols and ubiquinone, the major mitochondrial isoprenoid, are only slightly reduced in the single mutants. Although one functional FPS gene is sufficient to support isoprenoid biosynthesis for normal growth and development, the functions of FPS1 and FPS2 during development are not completely redundant. FPS1 activity has a predominant role during most of the plant life cycle, and FPS2 appears to have a major role in seeds and during the early stages of seedling development. Lack of FPS2 activity in seeds, but not of FPS1 activity, is associated with a marked reduction in sitosterol content and positive feedback regulation of 3-hydroxy-3-methylglutaryl CoA reductase activity that renders seeds hypersensitive to the 3-hydroxy-3-methylglutaryl CoA reductase inhibitor mevastatin.
authors.affiliation: Departament de Bioquímica i Biologia Molecular, Facultat de Farmàcia, Universitat de Barcelona, Avinguda Diagonal 643, 08028 Barcelona, SpainDepartment of Biology, Eidgenössische Technische Hochschule (ETH) Zurich, Universitätstrasse 2, 8092 Zurich, SwitzerlandInstitute of Organic Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
authors.forename: Marta
authors.initials: M
authors.lastname: Closa
authors.forename: Eva
authors.initials: E
authors.lastname: Vranová
authors.forename: Cristina
authors.initials: C
authors.lastname: Bortolotti
authors.forename: Laurent
authors.initials: L
authors.lastname: Bigler
authors.forename: Montserrat
authors.initials: M
authors.lastname: Arró
authors.forename: Albert
authors.initials: A
authors.lastname: Ferrer
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Gruissem
mesh_terms: D017360:Arabidopsis / Q000201:enzymology* / Q000235:genetics / Q000254:growth & development; D060406:Brassinosteroids / Q000378:metabolism; D017343:Genes, Plant; D051228:Geranyltranstransferase / Q000235:genetics / Q000378:metabolism*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D017368:Protein Prenylation; D013729:Terpenes / Q000378:metabolism*
chemical_list: D060406:Brassinosteroids; D007527:Isoenzymes; D013729:Terpenes; D051228:Geranyltranstransferase