Genomes and Genes
Summary: An enzyme that, in the pathway of cholesterol biosynthesis, catalyzes the condensation of isopentenyl pyrophosphate and dimethylallylpyrophosphate to yield pyrophosphate and geranylpyrophosphate. The enzyme then catalyzes the condensation of the latter compound with another molecule of isopentenyl pyrophosphate to yield pyrophosphate and farnesylpyrophosphate. EC 126.96.36.199.
- Schuller J, Zocher G, Liebhold M, Xie X, Stahl M, Li S, et al. Structure and catalytic mechanism of a cyclic dipeptide prenyltransferase with broad substrate promiscuity. J Mol Biol. 2012;422:87-99 pubmed publisher..Finally, nuclear magnetic resonance spectroscopy demonstrates that CdpNPT is a C-3 reverse PT that catalyzes the formation of C-3? prenylated indolines from diketopiperazines of tryptophan-containing cyclic dipeptides. ..
- Edwards D, Gerwick W. Lyngbyatoxin biosynthesis: sequence of biosynthetic gene cluster and identification of a novel aromatic prenyltransferase. J Am Chem Soc. 2004;126:11432-3 pubmed..LtxC was heterologously produced and purified from E. coli and shown to catalyze the transfer of a geranyl group to (-)-indolactam V as the final step in the biosynthesis of lyngbyatoxin A. ..
- Kumano T, Richard S, Noel J, Nishiyama M, Kuzuyama T. Chemoenzymatic syntheses of prenylated aromatic small molecules using Streptomyces prenyltransferases with relaxed substrate specificities. Bioorg Med Chem. 2008;16:8117-26 pubmed publisher..Kinetic studies with NphB reveal that the prenylation reaction follows a sequential ordered mechanism. ..
- Macone A, Lendaro E, Comandini A, Rovardi I, Matarese R, Carraturo A, et al. Chromane derivatives of small aromatic molecules: Chemoenzymatic synthesis and growth inhibitory activity on human tumor cell line LoVo WT. Bioorg Med Chem. 2009;17:6003-7 pubmed publisher..The chromane derivatives thus obtained were tested for cytotoxicity and pro-apoptotic activity using LoVo WT cells, a line of human colon adenocarcinoma. ..
- Jost M, Zocher G, Tarcz S, Matuschek M, Xie X, Li S, et al. Structure-function analysis of an enzymatic prenyl transfer reaction identifies a reaction chamber with modifiable specificity. J Am Chem Soc. 2010;132:17849-58 pubmed publisher..This finding provides support for a potential use of fungal indole prenyltransferases as modifiable bioreactors that can be engineered to catalyze highly specific prenyl transfer reactions. ..
- Yin W, Ruan H, Westrich L, Grundmann A, Li S. CdpNPT, an N-prenyltransferase from Aspergillus fumigatus: overproduction, purification and biochemical characterisation. Chembiochem. 2007;8:1154-61 pubmed..Interestingly, it shows significant sequence similarity to other indole prenyltransferases that catalyse the formation of C--C bonds. ..
- Heide L. Prenyl transfer to aromatic substrates: genetics and enzymology. Curr Opin Chem Biol. 2009;13:171-9 pubmed publisher..In fungi, a group of closely related indole prenyltransferase was found to carry out aromatic prenylations with different substrate specificity and regiospecificity, and to catalyze both regular and reverse prenylations. ..
- Liang P, Ko T, Wang A. Structure, mechanism and function of prenyltransferases. Eur J Biochem. 2002;269:3339-54 pubmed..For the enzymes involved in cyclic terpene biosynthesis, the structures and mechanisms of squalene cyclase, 5-epi-aristolochene synthase, pentalenene synthase, and trichodiene synthase are summarized. ..
- Kumano T, Tomita T, Nishiyama M, Kuzuyama T. Functional characterization of the promiscuous prenyltransferase responsible for furaquinocin biosynthesis: identification of a physiological polyketide substrate and its prenylated reaction products. J Biol Chem. 2010;285:39663-71 pubmed publisher..The promiscuous substrate specificity of Fur7 was demonstrated with respect to prenyl acceptor substrates and prenyl donor substrates. The steady-state kinetic constants of Fur7 with each prenyl acceptor substrate were also calculated. ..
- Xiao Y, Machacek M, Lee K, Kuzuyama T, Liu P. Prenyltransferase substrate binding pocket flexibility and its application in isoprenoid profiling. Mol Biosyst. 2009;5:913-7 pubmed publisher..This communication explores prenyltransferase substrate binding pocket flexibility to tag and enrich isoprenoids using affinity-based purification for metabolomic studies. ..
- Yellore V, Khan M, Bourla N, Rayner S, Chen M, Sonmez B, et al. Identification of mutations in UBIAD1 following exclusion of coding mutations in the chromosome 1p36 locus for Schnyder crystalline corneal dystrophy. Mol Vis. 2007;13:1777-82 pubmed..However, missense mutations in UBIAD1, located just outside of the originally described SCCD fine mapped region, were identified in each of the three families with SCCD, confirming that mutations in UBIAD1 are associated with SCCD. ..
- Schultz A, Lewis C, Luzung M, Baran P, Moore B. Functional characterization of the cyclomarin/cyclomarazine prenyltransferase CymD directs the biosynthesis of unnatural cyclic peptides. J Nat Prod. 2010;73:373-7 pubmed publisher..This knowledge was utilized to bioengineer novel derivatives of these marine bacterial natural products by providing synthetic N-alkyl tryptophans to a prenyltransferase-deficient mutant of Salinispora arenicola CNS-205. ..
- McGarvey T, Nguyen T, Malkowicz S. An interaction between apolipoprotein E and TERE1 with a possible association with bladder tumor formation. J Cell Biochem. 2005;95:419-28 pubmed..In conclusion, the results from this study suggest that the expression and regulation of the apoE pathway may yield clues toward understanding the function of TERE1. ..
- Bräuer L, Brandt W, Wessjohann L. Modeling the E. coli 4-hydroxybenzoic acid oligoprenyltransferase ( ubiA transferase) and characterization of potential active sites. J Mol Model. 2004;10:317-27 pubmed..Putative active amino acid residues and substrates are shown as capped sticks to describe their location and geometry in the putative active sites. The violet spheres identify Mg2+. ..
- Zocher G, Saleh O, Heim J, Herbst D, Heide L, Stehle T. Structure-based engineering increased the catalytic turnover rate of a novel phenazine prenyltransferase. PLoS ONE. 2012;7:e48427 pubmed publisher..This study therefore provides a solid foundation for additional enzyme modifications that should result in efficient, tailor-made biocatalysts for phenazines production. ..
- Jing Y, Liu C, Xu J, Wang L. A novel UBIAD1 mutation identified in a Chinese family with Schnyder crystalline corneal dystrophy. Mol Vis. 2009;15:1463-9 pubmed..Observations by in vivo laser scanning confocal microscopy and Fourier-domain OCT were consistent with the previous histopathologic descriptions of SCCD. ..
- Metzger U, Schall C, Zocher G, Uns ld I, Stec E, Li S, et al. The structure of dimethylallyl tryptophan synthase reveals a common architecture of aromatic prenyltransferases in fungi and bacteria. Proc Natl Acad Sci U S A. 2009;106:14309-14 pubmed publisher..These bacterial enzymes catalyze the prenylation of aromatic substrates in the biosynthesis of secondary metabolites (i.e., a reaction similar to that of DMATS)...
- Saleh O, Gust B, Boll B, Fiedler H, Heide L. Aromatic prenylation in phenazine biosynthesis: dihydrophenazine-1-carboxylate dimethylallyltransferase from Streptomyces anulatus. J Biol Chem. 2009;284:14439-47 pubmed publisher..The present finding extends the substrate range of this family, previously limited to phenolic compounds, to include also phenazine derivatives. ..
- Awakawa T, Fujita N, Hayakawa M, Ohnishi Y, Horinouchi S. Characterization of the biosynthesis gene cluster for alkyl-O-dihydrogeranyl-methoxyhydroquinones in Actinoplanes missouriensis. Chembiochem. 2011;12:439-48 pubmed publisher..missouriensis was found to produce 6-alkyl-4-O-dihydrogeranyl-2-methoxyhydroquinones derived from C(16-18) fatty acids by the function of the agq gene cluster. All of these prenylated phenolic lipids were novel compounds. ..
- Fredericks W, McGarvey T, Wang H, Lal P, Puthiyaveettil R, Tomaszewski J, et al. The bladder tumor suppressor protein TERE1 (UBIAD1) modulates cell cholesterol: implications for tumor progression. DNA Cell Biol. 2011;30:851-64 pubmed publisher..Elevated tumor cell cholesterol is known to affect apoptosis and growth signaling; thus, loss of TERE1 in invasive bladder cancer may represent a defect in menaquinone-mediated cholesterol homeostasis that contributes to progression. ..
- Kuzuyama T, Noel J, Richard S. Structural basis for the promiscuous biosynthetic prenylation of aromatic natural products. Nature. 2005;435:983-7 pubmed publisher..These crystal structures, coupled with in vitro assays, provide a basis for understanding and potentially manipulating the regio-specific prenylation of aromatic small molecules using this structurally unique family of aromatic PTases...
- Pojer F, Wemakor E, Kammerer B, Chen H, Walsh C, Li S, et al. CloQ, a prenyltransferase involved in clorobiocin biosynthesis. Proc Natl Acad Sci U S A. 2003;100:2316-21 pubmed..CloQ and the similar NovQ from the novobiocin producer seem to belong to a new class of prenyltransferases. ..
- Mugoni V, Postel R, Catanzaro V, De Luca E, Turco E, Digilio G, et al. Ubiad1 is an antioxidant enzyme that regulates eNOS activity by CoQ10 synthesis. Cell. 2013;152:504-18 pubmed publisher..These findings identify UBIAD1 as a nonmitochondrial CoQ10-forming enzyme with specific cardiovascular protective function via the modulation of eNOS activity...
- Weiss J, Wiaux C, Yellore V, Raber I, Eagle R, Mequio M, et al. Newly reported p.Asp240Asn mutation in UBIAD1 suggests central discoid corneal dystrophy is a variant of Schnyder corneal dystrophy. Cornea. 2010;29:777-80 pubmed publisher..This report underscores the utility of genetic testing in determining whether newly described corneal dystrophies are in fact unique entities or just variants of well-known diseases. ..
- McGarvey T, Nguyen T, Tomaszewski J, Monson F, Malkowicz S. Isolation and characterization of the TERE1 gene, a gene down-regulated in transitional cell carcinoma of the bladder. Oncogene. 2001;20:1042-51 pubmed..These data suggest a potential role for this gene product in the progression of bladder cancer. ..
- Yazaki K, Sasaki K, Tsurumaru Y. Prenylation of aromatic compounds, a key diversification of plant secondary metabolites. Phytochemistry. 2009;70:1739-45 pubmed publisher..Further relevant genes involved in the prenylation of other types of polyphenol are expected to be cloned by utilizing the sequence information provided by the above studies. ..
- Shindo K, Tachibana A, Tanaka A, Toba S, Yuki E, Ozaki T, et al. Production of novel antioxidative prenyl naphthalen-ols by combinational bioconversion with dioxygenase PhnA1A2A3A4 and prenyltransferase NphB or SCO7190. Biosci Biotechnol Biochem. 2011;75:505-10 pubmed..2-(2,3-Dihydroxyphenyl)-5,7-dihydroxy-chromen-4-one (2',3'-dihydroxychrysin) generated with another aromatic dihydroxylating dioxygenase and subsequent dehydrogenase was also geranylated at the C-5'-carbon by the action of NphB...
- Bonitz T, Alva V, Saleh O, Lupas A, Heide L. Evolutionary relationships of microbial aromatic prenyltransferases. PLoS ONE. 2011;6:e27336 pubmed publisher..In view of their homology and their similarities in structure and function, we propose to group the NphB and DMATS families together into a single superfamily, the PT-barrel superfamily. ..
- Nickerson M, Bosley A, Weiss J, Kostiha B, Hirota Y, Brandt W, et al. The UBIAD1 prenyltransferase links menaquinone-4 [corrected] synthesis to cholesterol metabolic enzymes. Hum Mutat. 2013;34:317-29 pubmed publisher..Our data suggest a role for endogenous MK-4 in maintaining cornea health and visual acuity. ..
- Ozaki T, Mishima S, Nishiyama M, Kuzuyama T. NovQ is a prenyltransferase capable of catalyzing the addition of a dimethylallyl group to both phenylpropanoids and flavonoids. J Antibiot (Tokyo). 2009;62:385-92 pubmed publisher..This study shows that NovQ can serve as a useful biocatalyst for the synthesis of prenylated phenylpropanoids and prenylated flavonoids. ..
- Botta B, Delle Monache G, Menendez P, Boffi A. Novel prenyltransferase enzymes as a tool for flavonoid prenylation. Trends Pharmacol Sci. 2005;26:606-8 pubmed
- Cui G, Li X, Merz K. Understanding the substrate selectivity and the product regioselectivity of Orf2-catalyzed aromatic prenylations. Biochemistry. 2007;46:1303-11 pubmed
- Haagen Y, Unsöld I, Westrich L, Gust B, Richard S, Noel J, et al. A soluble, magnesium-independent prenyltransferase catalyzes reverse and regular C-prenylations and O-prenylations of aromatic substrates. FEBS Lett. 2007;581:2889-93 pubmed..e. an unusual "reverse" prenylation. With 1,3-dihydroxynaphthalene and 4-hydroxybenzoate as substrates Fnq26 catalyzes O-prenylations. ..
- Orr A, Dube M, Marcadier J, Jiang H, Federico A, George S, et al. Mutations in the UBIAD1 gene, encoding a potential prenyltransferase, are causal for Schnyder crystalline corneal dystrophy. PLoS ONE. 2007;2:e685 pubmed..UBIAD1 may play a direct role in intracellular cholesterol biochemistry, or may prenylate other proteins regulating cholesterol transport and storage. ..
- Bräuer L, Brandt W, Schulze D, Zakharova S, Wessjohann L. A structural model of the membrane-bound aromatic prenyltransferase UbiA from E. coli. Chembiochem. 2008;9:982-92 pubmed publisher..The high similarity of the active fold of UbiA-transferase to that of 5-epi-aristolochene synthase (Nicotiana tabacum), despite a low homology, allows a hypothesis on a convergent evolution of these enzymes to be formed. ..
- Steffan N, Grundmann A, Yin W, Kremer A, Li S. Indole prenyltransferases from fungi: a new enzyme group with high potential for the production of prenylated indole derivatives. Curr Med Chem. 2009;16:218-31 pubmed..Diverse tryptophan derivatives and tryptophan-containing cyclic dipeptides were accepted by these enzymes, providing a new strategy for convenient production of biologically active substances, e.g. by chemoenzymatic synthesis. ..
- Saleh O, Haagen Y, Seeger K, Heide L. Prenyl transfer to aromatic substrates in the biosynthesis of aminocoumarins, meroterpenoids and phenazines: the ABBA prenyltransferase family. Phytochemistry. 2009;70:1728-38 pubmed publisher..Therefore, the enzymes of this family represent attractive tools for the chemoenzymatic synthesis of bioactive molecules. ..
- Seeger K, Flinspach K, Haug Schifferdecker E, Kulik A, Gust B, Fiedler H, et al. The biosynthetic genes for prenylated phenazines are located at two different chromosomal loci of Streptomyces cinnamonensis DSM 1042. Microb Biotechnol. 2011;4:252-62 pubmed publisher..The enzyme catalysed the prenylation of 5,10-dihydrophenazine-1-carboxylic acid (dihydro-PCA) using dimethylallyl diphosphate (DMAPP) as isoprenoid substrate. K(m) values were determined as 108 µM for dihydro-PCA and 25 µM for DMAPP. ..
- Fredericks W, Yin H, Lal P, Puthiyaveettil R, Malkowicz S, Fredericks N, et al. Ectopic expression of the TERE1 (UBIAD1) protein inhibits growth of renal clear cell carcinoma cells: altered metabolic phenotype associated with reactive oxygen species, nitric oxide and SXR target genes involved in cholesterol and lipid metabolism. Int J Oncol. 2013;43:638-52 pubmed publisher..Loss of TERE1 may contribute to the altered lipid metabolic phenotype associated with progression in RCC via an uncoupling of ROS/RNS and SXR signaling from apoptosis by elevation of cholesterol...
- McGarvey T, Nguyen T, Puthiyaveettil R, Tomaszewski J, Malkowicz S. TERE1, a novel gene affecting growth regulation in prostate carcinoma. Prostate. 2003;54:144-55 pubmed..Altogether, these data suggest that TERE1 maybe significant in prostate cancer growth regulation and the down regulation or absence of TERE1 may be an important component of the phenotype of advanced disease. ..
- Doisneau Sixou S, Cestac P, Chouini S, Carroll J, Hamilton A, Sebti S, et al. Contrasting effects of prenyltransferase inhibitors on estrogen-dependent cell cycle progression and estrogen receptor-mediated transcriptional activity in MCF-7 cells. Endocrinology. 2003;144:989-98 pubmed..However, they antagonize the ability of ER alpha to stimulate estrogen response element-dependent transcriptional activity, acting presumably through coregulator complex formation. ..
- Santos A, Lehmann R. Isoprenoids control germ cell migration downstream of HMGCoA reductase. Dev Cell. 2004;6:283-93 pubmed..The specificity and evolutionary conservation of the HMGCoAr pathway for germ cells suggest that an attractant common to invertebrates and vertebrates guides germ cells in early embryos. ..
- Li S. Applications of dimethylallyltryptophan synthases and other indole prenyltransferases for structural modification of natural products. Appl Microbiol Biotechnol. 2009;84:631-9 pubmed publisher..This feature of substrate flexibility was successfully used for regiospecific and stereospecific synthesis of different indole derivatives. ..
- Yin W, Grundmann A, Cheng J, Li S. Acetylaszonalenin biosynthesis in Neosartorya fischeri. Identification of the biosynthetic gene cluster by genomic mining and functional proof of the genes by biochemical investigation. J Biol Chem. 2009;284:100-9 pubmed publisher..Km values of AnaAT were determined for acetyl coenzyme A at 96 microm and for aszonalenin at 61 microm. The turnover numbers of the AnaPT and AnaAT reactions were determined at 1.5 and 0.14 s(-1), respectively. ..
- Mehta J, Vithana E, Venkataraman D, Venkatraman A, Yong V, Aung T, et al. Surgical management and genetic analysis of a Chinese family with the S171P mutation in the UBIAD1 gene, the gene for Schnyder corneal dystrophy. Br J Ophthalmol. 2009;93:926-31 pubmed publisher..This is the largest non-Caucasian pedigree described with SCD. Visual rehabilitation may be performed successfully with lamellar surgical procedures as opposed to full-thickness corneal grafts. ..
- Li S. Evolution of aromatic prenyltransferases in the biosynthesis of indole derivatives. Phytochemistry. 2009;70:1746-57 pubmed publisher..Diverse simple tryptophan derivatives and tryptophan-containing cyclic dipeptides were accepted by these enzymes, providing a strategy for convenient production of biologically active substances, e.g. by chemoenzymatic synthesis. ..
- Weiss J, Kruth H, Kuivaniemi H, Tromp G, White P, Winters R, et al. Mutations in the UBIAD1 gene on chromosome short arm 1, region 36, cause Schnyder crystalline corneal dystrophy. Invest Ophthalmol Vis Sci. 2007;48:5007-12 pubmed..Three candidate genes that may be involved in lipid metabolism and/or are expressed in the cornea were analyzed...
- Nakagawa K, Hirota Y, Sawada N, Yuge N, Watanabe M, Uchino Y, et al. Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme. Nature. 2010;468:117-21 pubmed publisher..Our results show that UBIAD1 is a human MK-4 biosynthetic enzyme; this identification will permit more effective decisions to be made about vitamin?K intake and bone health. ..
- Metzger U, Keller S, Stevenson C, Heide L, Lawson D. Structure and mechanism of the magnesium-independent aromatic prenyltransferase CloQ from the clorobiocin biosynthetic pathway. J Mol Biol. 2010;404:611-26 pubmed publisher..Since prenylation is thought to enhance the bioactivity of many natural products, CloQ offers considerable promise as a biocatalyst for the chemoenzymatic synthesis of novel compounds with therapeutic potential. ..
- Weiss J, Kruth H, Kuivaniemi H, Tromp G, Karkera J, Mahurkar S, et al. Genetic analysis of 14 families with Schnyder crystalline corneal dystrophy reveals clues to UBIAD1 protein function. Am J Med Genet A. 2008;146A:271-83 pubmed publisher..Protein analysis revealed structural and functional implications of SCCD mutations which may affect UBIAD1 function, ligand binding and interaction with binding partners, like apo E. ..
- Nickerson M, Kostiha B, Brandt W, Fredericks W, Xu K, Yu F, et al. UBIAD1 mutation alters a mitochondrial prenyltransferase to cause Schnyder corneal dystrophy. PLoS ONE. 2010;5:e10760 pubmed publisher..Mitochondrial UBIAD1 protein appears to have a highly conserved function that, at least in humans, is involved in cholesterol metabolism in a novel manner. ..
- Takahashi S, Takagi H, Toyoda A, Uramoto M, Nogawa T, Ueki M, et al. Biochemical characterization of a novel indole prenyltransferase from Streptomyces sp. SN-593. J Bacteriol. 2010;192:2839-51 pubmed publisher..Moreover, DeltaiptA mutants abolished the production of 6-DMAI-3-carbaldehyde as well as 6-dimethylallyl-L-Trp, suggesting that the iptA gene is involved in the production of 6-DMAI-3-carbaldehyde. ..
- Munakata R, Inoue T, Koeduka T, Sasaki K, Tsurumaru Y, Sugiyama A, et al. Characterization of coumarin-specific prenyltransferase activities in Citrus limon peel. Biosci Biotechnol Biochem. 2012;76:1389-93 pubmed..These findings provide information towards the discovery of a yet unidentified coumarin-specific prenyltransferase gene. ..
- Garcia Estrada C, Ullan R, Albillos S, Fernández Bodega M, Durek P, von Döhren H, et al. A single cluster of coregulated genes encodes the biosynthesis of the mycotoxins roquefortine C and meleagrin in Penicillium chrysogenum. Chem Biol. 2011;18:1499-512 pubmed publisher..All these genes are transcriptionally coregulated. Our results prove that roquefortine C and meleagrin derive from a single pathway. ..
- Sheares B, White S, Molowa D, Chan K, Ding V, Kroon P, et al. Cloning, analysis, and bacterial expression of human farnesyl pyrophosphate synthetase and its regulation in Hep G2 cells. Biochemistry. 1989;28:8129-35 pubmed..Lovastatin increases mRNA levels for farnesyl pyrophosphate synthetase 2.5-fold while mevalonic acid, low-density lipoprotein, and 25-hydroxycholesterol decrease mRNA levels to 40-50% of control values. ..
- Liu X, Hillwig M, Koharudin L, Gronenborn A. Unified biogenesis of ambiguine, fischerindole, hapalindole and welwitindolinone: identification of a monogeranylated indolenine as a cryptic common biosynthetic intermediate by an unusual magnesium-dependent aromatic prenyltransferase. Chem Commun (Camb). 2016;52:1737-40 pubmed publisher
- Saikia S, Parker E, Koulman A, Scott B. Four gene products are required for the fungal synthesis of the indole-diterpene, paspaline. FEBS Lett. 2006;580:1625-30 pubmed
- Tao W, Shi J, Zhang Q, Xue B, Sun Y, Li C. Egr-1 enhances drug resistance of breast cancer by modulating MDR1 expression in a GGPPS-independent manner. Biomed Pharmacother. 2013;67:197-202 pubmed publisher..Indeed, our results suggest a novel pathway by which paclitaxel induces MDR1 expression, possibly illuminating a potential target pathway for the prevention of MDR1-mediated drug resistance. ..