Hmdb loader
Identification
HMDB Protein ID HMDBP12632
Secondary Accession Numbers None
Name Oxidoreductase asL5
Synonyms
  1. Xenovulene A biosynthesis cluster protein L5
Gene Name ASL5
Protein Type Unknown
Biological Properties
General Function Not Available
Specific Function Oxidoreductase; part of the gene cluster that mediates the biosynthesis of xenovulene A, an unusual meroterpenoid that has potent inhibitory effects on the human gamma-aminobutyrate A (GABAA) benzodiazepine receptor (PubMed:29773797). The first step of xenovulene A biosynthesis is the biosynthesis of 3-methylorcinaldehyde performed by the non-reducing polyketide synthase aspks1 (PubMed:17912413, PubMed:29773797, PubMed:20552126). The salicylate hydroxylase asL1 then catalyzes the oxidative dearomatization of 3-methylorcinaldehyde to yield a dearomatized hydroxycyclohexadione (PubMed:29773797). The 2-oxoglutarate-dependent dioxygenase asL3 further catalyzes the oxidative ring expansion to provide the first tropolone metabolite (PubMed:29773797). The cytochrome P450 monooxygenase asR2 allows the synthesis of tropolone hemiacetal (PubMed:29773797). In parallel, a previously unrecognised class of terpene cyclase, asR6, produces alpha-humulene from farnesylpyrophosphate (FPP) (PubMed:29773797). The putative Diels-Alderase asR5 probably catalyzes the formation of the tropolone-humulene skeleton by linking humulene and the polyketide moiety (PubMed:29773797). Oxidative-ring contractions catalyzed by asL4 and asL6 then processively remove carbon atoms from the polyketide to yield xenovulene A (PubMed:29773797).
Pathways Not Available
Reactions Not Available
GO Classification
Molecular Function
oxidoreductase activity
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 Not Available
Molecular Weight 25469.86
Theoretical pI Not Available
Pfam Domain Function Not Available
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence Not Available
GenBank ID Protein Not Available
UniProtKB/Swiss-Prot ID A0A2U8U2K8
UniProtKB/Swiss-Prot Entry Name ASL5_SARSH
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. Bailey AM, Cox RJ, Harley K, Lazarus CM, Simpson TJ, Skellam E: Characterisation of 3-methylorcinaldehyde synthase (MOS) in Acremonium strictum: first observation of a reductive release mechanism during polyketide biosynthesis. Chem Commun (Camb). 2007 Oct 21;(39):4053-5. doi: 10.1039/b708614h. Epub 2007 Jul 25. [PubMed:17912413 ]
  2. Schor R, Schotte C, Wibberg D, Kalinowski J, Cox RJ: Three previously unrecognised classes of biosynthetic enzymes revealed during the production of xenovulene A. Nat Commun. 2018 May 17;9(1):1963. doi: 10.1038/s41467-018-04364-9. [PubMed:29773797 ]
  3. Thomas P, Sundaram H, Krishek BJ, Chazot P, Xie X, Bevan P, Brocchini SJ, Latham CJ, Charlton P, Moore M, Lewis SJ, Thornton DM, Stephenson FA, Smart TG: Regulation of neuronal and recombinant GABA(A) receptor ion channels by xenovulene A, a natural product isolated from Acremonium strictum. J Pharmacol Exp Ther. 1997 Aug;282(2):513-20. [PubMed:9262310 ]
  4. Fisch KM, Skellam E, Ivison D, Cox RJ, Bailey AM, Lazarus CM, Simpson TJ: Catalytic role of the C-terminal domains of a fungal non-reducing polyketide synthase. Chem Commun (Camb). 2010 Aug 7;46(29):5331-3. doi: 10.1039/c0cc01162b. Epub 2010 Jun 16. [PubMed:20552126 ]