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Showing Protein Polyprenyl transferase pyr6 (HMDBP14144)

IdentificationBiological propertiesGene propertiesProtein propertiesExternal linksReferencesXMLShow 0 metabolites
Identification
HMDB Protein ID HMDBP14144
Secondary Accession Numbers None
Name Polyprenyl transferase pyr6
Synonyms
  1. Pyripyropene synthesis protein 6
Gene Name PYR6
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Polyprenyl transferase; part of the gene cluster that mediates the biosynthesis of pyripyropene A, a specific human acyl-coenzyme A:cholesterol acyltransferase 2 inhibitor (PubMed:20861902). The first step of the pathway is the synthesis of nicotinyl-CoA from nicotinic acid by the nicotinic acid-CoA ligase pyr1 (PubMed:20861902). Nicotinyl-CoA is then a substrate of polyketide synthase pyr2 to produce 4-hydroxy-6-(3-pyridinyl)-2H-pyran-2-one (HPPO) which is further prenylated by the polyprenyl transferase pyr6 to yield farnesyl-HPPO (PubMed:20861902). The next steps consist of an epoxidation of farnesyl-HPPO to epoxyfarnesyl-HPPO by FAD-dependent monooxygenase pyr5 and a cyclization of the terpenoid portion by the terpene cyclase pyr4 to yield deacetyl-pyripyropene E (PubMed:20861902). The 2 cytochrome P450 monooxygenases pyr3 and pyr9, and the 2 acetyltransferases pyr7 and pyr8 are involved in the conversion of deacetyl-pyripyropene E into pyripyropene A through several cycles of oxidation and acetylation steps (PubMed:20861902). Pyr7 acetylates deacetyl-pyripyropene E to pyripyropene E which is oxidized to 11-deacetyl-pyripyropene O by pyr3, which is in turn acetylated into pyripyropene O by pyr8 (PubMed:21224862, PubMed:26019565). Pyripyropene O is then oxidized to deacetyl-pyripyropene A by pyr9 (PubMed:21224862). Deacetyl-pyripyropene A is finally acetylated to pyripyropene A by pyr8 (PubMed:26019565).
Pathways
  • terpenoid biosynthesis
Reactions Not Available
GO Classification
Biological Process
ubiquinone biosynthetic process
terpenoid biosynthetic process
Cellular Component
integral to mitochondrial inner membrane
Molecular Function
4-hydroxybenzoate octaprenyltransferase activity
transferase activity, transferring alkyl or aryl (other than methyl) groups
Cellular Location Not Available
Gene Properties
Chromosome Location Not Available
Locus Not Available
SNPs Not Available
Gene Sequence Not Available
Protein Properties
Number of Residues 320
Molecular Weight 35776.355
Theoretical pI 8.315
Pfam Domain Function
Signals Not Available
Transmembrane Regions
  • 22-42;60-80;101-121;127-147;155-175;186-206;233-253;260-280;296-316;
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID Q4WLD0
UniProtKB/Swiss-Prot Entry Name PYR6_ASPFU
PDB IDs Not Available
GenBank Gene ID Not Available
GeneCard ID Not Available
GenAtlas ID Not Available
HGNC ID Not Available
References
General References
  1. Nierman WC, Pain A, Anderson MJ, Wortman JR, Kim HS, Arroyo J, Berriman M, Abe K, Archer DB, Bermejo C, Bennett J, Bowyer P, Chen D, Collins M, Coulsen R, Davies R, Dyer PS, Farman M, Fedorova N, Fedorova N, Feldblyum TV, Fischer R, Fosker N, Fraser A, Garcia JL, Garcia MJ, Goble A, Goldman GH, Gomi K, Griffith-Jones S, Gwilliam R, Haas B, Haas H, Harris D, Horiuchi H, Huang J, Humphray S, Jimenez J, Keller N, Khouri H, Kitamoto K, Kobayashi T, Konzack S, Kulkarni R, Kumagai T, Lafon A, Latge JP, Li W, Lord A, Lu C, Majoros WH, May GS, Miller BL, Mohamoud Y, Molina M, Monod M, Mouyna I, Mulligan S, Murphy L, O'Neil S, Paulsen I, Penalva MA, Pertea M, Price C, Pritchard BL, Quail MA, Rabbinowitsch E, Rawlins N, Rajandream MA, Reichard U, Renauld H, Robson GD, Rodriguez de Cordoba S, Rodriguez-Pena JM, Ronning CM, Rutter S, Salzberg SL, Sanchez M, Sanchez-Ferrero JC, Saunders D, Seeger K, Squares R, Squares S, Takeuchi M, Tekaia F, Turner G, Vazquez de Aldana CR, Weidman J, White O, Woodward J, Yu JH, Fraser C, Galagan JE, Asai K, Machida M, Hall N, Barrell B, Denning DW: Genomic sequence of the pathogenic and allergenic filamentous fungus Aspergillus fumigatus. Nature. 2005 Dec 22;438(7071):1151-6. doi: 10.1038/nature04332. [PubMed:16372009 ]
  2. Wang HJ, Gloer JB, Wicklow DT, Dowd PF: Aflavinines and other antiinsectan metabolites from the ascostromata of Eupenicillium crustaceum and related species. Appl Environ Microbiol. 1995 Dec;61(12):4429-35. doi: 10.1128/aem.61.12.4429-4435.1995. [PubMed:8534106 ]
  3. Ohshiro T, Ohte S, Matsuda D, Ohtawa M, Nagamitsu T, Sunazuka T, Harigaya Y, Rudel LL, Omura S, Tomoda H: Selectivity of pyripyropene derivatives in inhibition toward acyl-CoA:cholesterol acyltransferase 2 isozyme. J Antibiot (Tokyo). 2008 Aug;61(8):503-8. doi: 10.1038/ja.2008.67. [PubMed:18997389 ]
  4. Hayashi A, Arai M, Fujita M, Kobayashi M: Pyripyropenes, fungal sesquiterpenes conjugated with alpha-pyrone and pyridine moieties, exhibits anti-angiogenic activity against human umbilical vein endothelial cells. Biol Pharm Bull. 2009 Jul;32(7):1261-5. doi: 10.1248/bpb.32.1261. [PubMed:19571395 ]
  5. Hu J, Okawa H, Yamamoto K, Oyama K, Mitomi M, Anzai H: Characterization of two cytochrome P450 monooxygenase genes of the pyripyropene biosynthetic gene cluster from Penicillium coprobium. J Antibiot (Tokyo). 2011 Mar;64(3):221-7. doi: 10.1038/ja.2010.162. Epub 2011 Jan 12. [PubMed:21224862 ]
  6. Hu J, Furutani A, Yamamoto K, Oyama K, Mitomi M, Anzai H: Characterization of two acetyltransferase genes in the pyripyropene biosynthetic gene cluster from Penicillium coprobium. Biotechnol Biotechnol Equip. 2014 Sep 3;28(5):818-826. doi: 10.1080/13102818.2014.960140. Epub 2014 Oct 31. [PubMed:26019565 ]
  7. Itoh T, Tokunaga K, Matsuda Y, Fujii I, Abe I, Ebizuka Y, Kushiro T: Reconstitution of a fungal meroterpenoid biosynthesis reveals the involvement of a novel family of terpene cyclases. Nat Chem. 2010 Oct;2(10):858-64. doi: 10.1038/nchem.764. Epub 2010 Aug 1. [PubMed:20861902 ]