13058-04-3Relevant articles and documents
THE ABSOLUTE STEREOCHEMISTRY OF THE ENZYMIC CYCLISATION TO FORM THE STERPURENE SESQUITERPENES
Abell, Chris,Leech, Andrew P.
, p. 4337 - 4340 (1988)
Incorporation studies using acetate into a novel sterpurene sesquiterpene, 9,12-dihydroxysterpurene (1), have allowed the absolute stereochemistry of the enzymic cyclisation of farnesyl pyrophosphate to sterpurene to be elucidated.Observation of two-bond 13C-13C coupling across the cyclobutane ring confirms the derivation of these two carbon atoms from the same acetate unit.
Biosynthesis of isoprenoids in Escherichia coli: stereochemistry of the reaction catalyzed by farnesyl diphosphate synthase.
Leyes,Baker,Poulter
, p. 1071 - 1073 (1999)
[formula: see text] Farnesyl diphosphate (FPP) synthase from Escherichia coli catalyzes the condensation of isopentenyl diphosphate (IPP) and geranyl diphosphate (GPP) with selective removal of the pro-R hydrogen at C2 of IPP, the same stereochemistry observed for the pig liver, yeast, and avian enzymes.
Mycobacterium tuberculosis H37Rv3377c encodes the diterpene cyclase for producing the halimane skeleton
Nakano, Chiaki,Okamura, Tomoo,Sato, Tsutomu,Dairi, Tohru,Hoshino, Tsutomu
, p. 1016 - 1018 (2005)
The cloning and functional expression of Mycobacterium tuberculosis Rv3377c in Escherichia coli revealed that this gene encodes the diterpene cyclase for producing (+)-5(6),13-halimadiene-15-ol, which accepts geranylgeranyldiphosphate as the intrinsic substrate. The Royal Society of Chemistry 2005.
Incorporation of farnesyl pyrophosphate derivertives into abscisic acid and its biosynthetic intermediates in Cercospora cruenta
Yamamoto, Hirotaka,Oritani, Takayuki
, p. 821 - 824 (1997)
To investigate the transformation from (2E,6E)-farnesyl pyrophosphate to (2Z,4E)-γ-ionylideneethanol in the abscisic acid-producing fungi, Cercospora cruenta, plausible [2-14C]-C15 intermediates were prepared and fed. Substrates such as (2E,6E)-farnesyl pyrophosphate, (2Z,4E)-γ-ionylideneethanol and its pyrophosphate were incorporated into ABA and its known biosynthetic precursors. It is suggested that (2E,6E)-farnesyl pyrophosphate is converted to (2Z,4E)-γ-ionylideneethanol in four consecutive steps: dehydrogenation, isomerization, cyclization and hydrolysis.
Cloning and characterization of isoprenyl diphosphate synthases with farnesyl diphosphate and geranylgeranyl diphosphate synthase activity from Norway spruce (Picea abies) and their relation to induced oleoresin formation
Schmidt, Axel,Gershenzon, Jonathan
, p. 2649 - 2659 (2007)
The conifer Picea abies (Norway spruce) employs terpenoid-based oleoresins as part of its constitutive and induced defense responses to herbivores and pathogens. The isoprenyl diphosphate synthases are branch-point enzymes of terpenoid biosynthesis leading to the various terpene classes. We isolated three genes encoding isoprenyl diphosphate synthases from P. abies cDNA libraries prepared from the bark and wood of methyl jasmonate-treated saplings and screened via a homology-based PCR approach using degenerate primers. Enzyme assays of the purified recombinant proteins expressed in Escherichia coli demonstrated that one gene (PaIDS 4) encodes a farnesyl diphosphate synthase and the other two (PaIDS 5 and PaIDS 6) encode geranylgeranyl diphosphate synthases. The sequences have moderate similarity to those of farnesyl diphosphate and geranylgeranyl diphosphate synthases already known from plants, and the kinetic properties of the enzymes are not unlike those of other isoprenyl diphosphate synthases. Of the three genes, only PaIDS 5 displayed a significant increase in transcript level in response to methyl jasmonate spraying, suggesting its involvement in induced oleoresin biosynthesis.
Synthesis of geranyl S-thiolodiphosphate. A new alternative substrate/inhibitor for prenyltransferases.
Phan,Poulter
, p. 2287 - 2289 (2000)
The tris(tetra-n-butylammonium) salt of thiopyrophosphate 5 was prepared from trimethyl phosphate in four steps. Treatment of geranyl bromide with 5 gave an 80% yield of geranyl S-thiolodiphosphate (6). Thiolodiphosphate 6 is substantially less reactive than geranyl diphosphate (7) in the prenyl transfer reaction catalyzed by farnesyl diphosphate synthase and is a good inhibitor of the enzyme.
Tris(tetra-n-butylammonium) hydrogen pyrophosphate. A new reagent for the preparation of allylic pyrophosphate esters [3]
Dixit, Vyas M.,Laskovics, F. Mark,Noall, Wendy I.,Poulter, C. Dale
, p. 1967 - 1969 (1981)
Tris(tetra-n-butylammonium) hydrogen pyrophosphate was used to prepare dimethylallyl pyrophosphate (1-OPP), 7-methylocta-2,6-dien-1-yl pyrophosphate (2-OPP), geranyl pyrophosphate (3-OPP), 2-flourogeranyl pyrophosphate (4-OPP), and farnesyl pyrophosphate (5-OPP) from the corresponding alcohols in moderate yields by a two-step sequence via the corresponding primary, allylic bromides.
Mutation of archaeal isopentenyl phosphate kinase highlights mechanism and guides phosphorylation of additional isoprenoid monophosphates
Dellas, Nikki,Noel, Joseph P.
, p. 589 - 601 (2010)
The biosynthesis of isopentenyl diphosphate (IPP) from either the mevalonate (MVA) or the 1-deoxy-d-xylulose 5-phosphate (DXP) pathway provides the key metabolite for primary and secondary isoprenoid biosynthesis. Isoprenoid metabolism plays crucial roles in membrane stability, steroid biosynthesis, vitamin production, protein localization, defense and communication, photoprotection, sugar transport, and glycoprotein biosynthesis. Recently, an alternative branch of the MVA pathway was discovered in the archaeon Methanocaldococcus jannaschii involving a small molecule kinase, isopentenyl phosphate kinase (IPK). IPK belongs to the amino acid kinase (AAK) superfamily. In vitro, IPK phosphorylates isopentenyl monophosphate (IP) in an ATP and Mg2+-dependent reaction producing IPP. Here, we describe crystal structures of IPK from M. jannaschii refined to nominal resolutions of 2.0-2.8 A. Notably, an active site histidine residue (His60) forms a hydrogen bond with the terminal phosphate of both substrate and product. This His residue serves as a marker for a subset of the AAK family that catalyzes phosphorylation of phosphate or phosphonate functional groups; the larger family includes carboxyl-directed kinases, which lack this active site residue. Using steady-state kinetic analysis of H60A, H60N, and H60Q mutants, the protonated form of the Nε2 nitrogen of His60 was shown to be essential for catalysis, most likely through hydrogen bond stabilization of the transition state accompanying transphosphorylation. Moreover, the structures served as the starting point for the engineering of IPK mutants capable of the chemoenzymatic synthesis of longer chain isoprenoid diphosphates from monophosphate precursors.
Structure-based protein engineering enables prenyl donor switching of a fungal aromatic prenyltransferase
Mai, Peter,Zocher, Georg,Stehle, Thilo,Li, Shu-Ming
, p. 7461 - 7469 (2018)
Microorganisms provide valuable enzyme machinery to assemble complex molecules. Fungal prenyltransferases (PTs) typically catalyse highly regiospecific prenylation reactions that are of significant pharmaceutical interest. While the majority of PTs accepts dimethylallyl diphosphate (DMAPP), very few such enzymes can use geranyl diphosphate (GPP) or farnesyl diphosphate (FPP) as donors. This catalytic gap prohibits the wide application of PTs for structural diversification. Structure-guided molecular modelling and site-directed mutagenesis of FgaPT2 from Aspergillus fumigatus led to the identification of the gatekeeping residue Met328 responsible for the prenyl selectivity and sets the basis for creation of GPP- and FPP-accepting enzymes. Site-saturation mutagenesis of the gatekeeping residue at position 328 in FgaPT2 revealed that the size of this side chain is the determining factor for prenyl selectivity, while its hydrophobicity is crucial for allowing DMAPP and GPP to bind.
Farnesyl Diphosphate Synthase Reactions of Geranyl Diphosphate Analogues Having Oxygen Atoms in Their Alkyl Chains
Maki, Yuji,Satoh, Hikaru,Kurihara, Masayo,Endo, Takae,Watanabe, Gotaro,Ogura, Kyozo
, p. 1841 - 1844 (1994)
Seven geranyl diphosphate analogues having oxygen atoms in their alkyl chains were synthesized and examined for their reactivities as substrates in the reaction catalyzed by pig liver farnesyl diphosphate synthase.All of these compounds acted as substrates to give farnesyl diphosphate analogues.It was suggested that the enzyme cavity for the geranyl moiety is tolerant enough to accommodate alkyl moietes containing oxygen atoms.
