Identification |
HMDB Protein ID
| HMDBP12639 |
Secondary Accession Numbers
| None |
Name
| Salicylate hydroxylase asL1 |
Synonyms
|
- FAD-dependent monooxygenase asL1
- Xenovulene A biosynthesis cluster protein L1
|
Gene Name
| ASL1 |
Protein Type
| Unknown |
Biological Properties |
General Function
| Not Available |
Specific Function
| Salicylate hydroxylase; 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
|
|
Reactions
| Not Available |
GO Classification
|
Biological Process |
terpenoid biosynthetic process |
Cellular Component |
integral to membrane |
Molecular Function |
monooxygenase activity |
FAD binding |
|
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
| 53344.835 |
Theoretical pI
| Not Available |
Pfam Domain Function
|
|
Signals
|
Not Available
|
Transmembrane Regions
|
|
Protein Sequence
|
Not Available
|
External Links |
GenBank ID Protein
| Not Available |
UniProtKB/Swiss-Prot ID
| A0A2U8U2L6 |
UniProtKB/Swiss-Prot Entry Name
| ASL1_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
| - 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 ]
- 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 ]
- 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 ]
- 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 ]
|