A0A1P8VF85 · PIGH_MONRU
- ProteinDehydrogenase pigH
- GenepigH
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids369 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score3/5
Function
function
Dehydrogenase; part of the gene cluster that mediates the biosynthesis of azaphilone pigments (MonAzPs), a complex mixture of compounds with a common azaphilone skeleton very widely used as food colorants (PubMed:26946170, PubMed:28959415, PubMed:34220766).
Within the pathway, pigH might be involved in the late steps of yellow pigments monascin and ankaflavin biosynthesis (PubMed:28959415).
The first step of the pathway is performed by the nrPKS pigA that forms the hexaketide precursor from successive condensations of five malonyl-CoA units, with a simple acetyl-CoA starter unit. The role of esterase pigG is not clear, but it may play at most a supplementary role in the formation of the benzaldehyde produced by the pigA nrPKS. This very reactive benzaldehyde is intercepted by the pigC ketoreductase that to provide the first stable enzyme-free MonAzPs intermediate, 6-(4-hydroxy-2-oxopentyl)-3-methyl-2,4-dioxocyclohexane carbaldehyde, also known as M7PKS-1. The FAD-dependent monooxygenase pigN hydroxylates M7PKS-1 at C-4, which triggers the formation of the pyran ring. PigJ, pigK and pigD are involved in the acetylation of the pyran ring. PigJ and pigK form the two subunits of a dedicated fungal FAS that produces the side chain fatty acyl moiety of MonAzPs and pigD transfers the fatty acyl chain to the C-4 alcohol. PigM and pigO are involved in the elimination of the omega-1 alcohol. PigM acts as an O-acetyltransferase that synthesizes the putative O-11 acetyl intermediate whereas pigO eliminates acetic acid to yield an intermediate with a C1011 double bond. The dehydration of the C-11 alcohol followed by the reduction of the C67 double bond by the NAD(P)H-dependent oxidoreductase pigE increases the electrophilicity of the C-5 ketone of the resulting acyl benzopyran. This in turn sets up the C-5 ketone for an intramolecular Knoevenagel aldol condensation with the C-20 enol of the side chain. This condensation affords the characteristic linear tricyclic carbon skeletons of the yellow pigments that serve as the common precursors for the classical yellow pigments monascin and ankaflavin, orange pigments rubopunctatin and monascorubrin, and red pigments ribropunctamine and monascorubramine. The FAD-dependent oxidoreductase pigF is especially invoved in the biosynthesis of orange and red pigments via desaturation of C67 (PubMed:28959415).
Within the pathway, pigH might be involved in the late steps of yellow pigments monascin and ankaflavin biosynthesis (PubMed:28959415).
The first step of the pathway is performed by the nrPKS pigA that forms the hexaketide precursor from successive condensations of five malonyl-CoA units, with a simple acetyl-CoA starter unit. The role of esterase pigG is not clear, but it may play at most a supplementary role in the formation of the benzaldehyde produced by the pigA nrPKS. This very reactive benzaldehyde is intercepted by the pigC ketoreductase that to provide the first stable enzyme-free MonAzPs intermediate, 6-(4-hydroxy-2-oxopentyl)-3-methyl-2,4-dioxocyclohexane carbaldehyde, also known as M7PKS-1. The FAD-dependent monooxygenase pigN hydroxylates M7PKS-1 at C-4, which triggers the formation of the pyran ring. PigJ, pigK and pigD are involved in the acetylation of the pyran ring. PigJ and pigK form the two subunits of a dedicated fungal FAS that produces the side chain fatty acyl moiety of MonAzPs and pigD transfers the fatty acyl chain to the C-4 alcohol. PigM and pigO are involved in the elimination of the omega-1 alcohol. PigM acts as an O-acetyltransferase that synthesizes the putative O-11 acetyl intermediate whereas pigO eliminates acetic acid to yield an intermediate with a C1011 double bond. The dehydration of the C-11 alcohol followed by the reduction of the C67 double bond by the NAD(P)H-dependent oxidoreductase pigE increases the electrophilicity of the C-5 ketone of the resulting acyl benzopyran. This in turn sets up the C-5 ketone for an intramolecular Knoevenagel aldol condensation with the C-20 enol of the side chain. This condensation affords the characteristic linear tricyclic carbon skeletons of the yellow pigments that serve as the common precursors for the classical yellow pigments monascin and ankaflavin, orange pigments rubopunctatin and monascorubrin, and red pigments ribropunctamine and monascorubramine. The FAD-dependent oxidoreductase pigF is especially invoved in the biosynthesis of orange and red pigments via desaturation of C67 (PubMed:28959415).
Biotechnology
As colorants, MonAzPs are widely used in various food products for centuries (PubMed:37087240).
Moreover, MonAzPs also possess wide-ranging biological activities such as antibacterial activity, preventing hypertension, lowering cholesterol levels, causing hypolipidemic effects, and displaying antiobesity and antitumor activities (PubMed:16283302, PubMed:16660141, PubMed:17191930, PubMed:20666456, PubMed:22562164).
Moreover, MonAzPs also possess wide-ranging biological activities such as antibacterial activity, preventing hypertension, lowering cholesterol levels, causing hypolipidemic effects, and displaying antiobesity and antitumor activities (PubMed:16283302, PubMed:16660141, PubMed:17191930, PubMed:20666456, PubMed:22562164).
Pathway
Secondary metabolite biosynthesis.
Features
Showing features for binding site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | membrane | |
Molecular Function | nucleotide binding | |
Molecular Function | oxidoreductase activity, acting on NAD(P)H | |
Molecular Function | pigment binding |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameDehydrogenase pigH
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Eurotiomycetes > Eurotiomycetidae > Eurotiales > Aspergillaceae > Monascus
Accessions
- Primary accessionA0A1P8VF85
Subcellular Location
UniProt Annotation
GO Annotation
Membrane ; Single-pass membrane protein
Features
Showing features for transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Transmembrane | 280-300 | Helical | ||||
Sequence: TIIFFVSWIISFKFKGLLKGI |
Keywords
- Cellular component
Phenotypes & Variants
PTM/Processing
Features
Showing features for chain, glycosylation.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000460215 | 1-369 | Dehydrogenase pigH | |||
Sequence: MPTNRAAWQPAKKAPLLEVKAAPYPPPKANRIVVKNGAVAVNPIDWLIQSKGDIMFTWLKYPFVLGSDVAGEVVEVGKNVTRFQVGDRVLGFARGTDEKVNDSSEGAFQEYTVLVPDLTAHIPSSLSFESAAVIPLGLATAGAGLFQQDQLGLQLPTSPARPPTGQTVLIWGGSTSVGSNAIQLAVAAGYEVFTTASRKNFEYAAKLGAAKVFDYRSGSVTQDIIRAFKGRTSAGALAIGQGGAEACMEVLDHVQGRKFIALASYPVPQEEPKRLVMLRTIIFFVSWIISFKFKGLLKGIKSNFIFATSVNHNGIGKALFVDFLPDALRAGEFVPAPDAQVAGKGLESIQTAFEQQKQGVSAKKIVVSL | ||||||
Glycosylation | 79 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N | ||||||
Glycosylation | 101 | N-linked (GlcNAc...) asparagine | ||||
Sequence: N |
Keywords
- PTM
Expression
Induction
Expression is positively regulated by the azaphilone pigments (MonAzPs) gene cluster-specific transcription regulator pigB.
Structure
Family & Domains
Features
Showing features for domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 13-367 | Enoyl reductase (ER) | ||||
Sequence: KAPLLEVKAAPYPPPKANRIVVKNGAVAVNPIDWLIQSKGDIMFTWLKYPFVLGSDVAGEVVEVGKNVTRFQVGDRVLGFARGTDEKVNDSSEGAFQEYTVLVPDLTAHIPSSLSFESAAVIPLGLATAGAGLFQQDQLGLQLPTSPARPPTGQTVLIWGGSTSVGSNAIQLAVAAGYEVFTTASRKNFEYAAKLGAAKVFDYRSGSVTQDIIRAFKGRTSAGALAIGQGGAEACMEVLDHVQGRKFIALASYPVPQEEPKRLVMLRTIIFFVSWIISFKFKGLLKGIKSNFIFATSVNHNGIGKALFVDFLPDALRAGEFVPAPDAQVAGKGLESIQTAFEQQKQGVSAKKIVV |
Sequence similarities
Belongs to the zinc-containing alcohol dehydrogenase family.
Keywords
- Domain
Family and domain databases
Sequence
- Sequence statusComplete
- Length369
- Mass (Da)39,423
- Last updated2017-04-12 v1
- ChecksumB2ADADF98A913F2B