A0A1D5AG16 · PIGJ_MONRU
- ProteinFatty acid synthase alpha subunit pigJ
- GenepigJ
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1842 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Fatty acid synthase alpha subunit; 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).
PigJ and pigK form the two subunits of a dedicated fungal fatty acid synthase (FAS) that produces the side chain fatty acyl moiety of MonAzPs, a beta-keto fatty acid. The chain length control of the pigJ-pigK FAS is somewhat flexible as MonAzPs features either a beta-ketooctanoic or a beta-ketodecanoic acid moiety. The beta-ketoacyl-ACP probably serves as the substrate for the acetyltransferase pigD that directly transfers the fatty acyl chain to the C-4 alcohol of the pyran ring (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).
PigJ and pigK form the two subunits of a dedicated fungal fatty acid synthase (FAS) that produces the side chain fatty acyl moiety of MonAzPs, a beta-keto fatty acid. The chain length control of the pigJ-pigK FAS is somewhat flexible as MonAzPs features either a beta-ketooctanoic or a beta-ketodecanoic acid moiety. The beta-ketoacyl-ACP probably serves as the substrate for the acetyltransferase pigD that directly transfers the fatty acyl chain to the C-4 alcohol of the pyran ring (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).
Catalytic activity
- a fatty acyl-[ACP] + H+ + malonyl-[ACP] = a 3-oxoacyl-[ACP] + CO2 + holo-[ACP]
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 active site, binding site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Active site | 1244 | For beta-ketoacyl synthase activity | ||||
Sequence: C | ||||||
Active site | 1470 | For beta-ketoacyl synthase activity | ||||
Sequence: H | ||||||
Active site | 1511 | For beta-ketoacyl synthase activity | ||||
Sequence: H | ||||||
Binding site | 1725 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Binding site | 1725-1727 | acetyl-CoA (UniProtKB | ChEBI) | ||||
Sequence: DVE | ||||||
Binding site | 1726 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: V | ||||||
Binding site | 1727 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: E | ||||||
Binding site | 1761 | acetyl-CoA (UniProtKB | ChEBI) | ||||
Sequence: S | ||||||
Binding site | 1770-1780 | acetyl-CoA (UniProtKB | ChEBI) | ||||
Sequence: EAVFKSLQTPS | ||||||
Binding site | 1823-1825 | acetyl-CoA (UniProtKB | ChEBI) | ||||
Sequence: ITH | ||||||
Binding site | 1824 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Binding site | 1825 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: H |
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | fatty acid synthase complex | |
Molecular Function | 3-oxoacyl-[acyl-carrier-protein] reductase (NADPH) activity | |
Molecular Function | 3-oxoacyl-[acyl-carrier-protein] synthase activity | |
Molecular Function | fatty acid synthase activity | |
Molecular Function | holo-[acyl-carrier-protein] synthase activity | |
Molecular Function | magnesium ion binding | |
Molecular Function | pigment binding | |
Biological Process | long-chain fatty acid biosynthetic process |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameFatty acid synthase alpha subunit pigJ
- EC number
Including 2 domains:
- Recommended name3-oxoacyl-[acyl-carrier-protein] reductase
- EC number
- Alternative names
- Recommended name3-oxoacyl-[acyl-carrier-protein] synthase
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Fungi > Dikarya > Ascomycota > Pezizomycotina > Eurotiomycetes > Eurotiomycetidae > Eurotiales > Aspergillaceae > Monascus
Accessions
- Primary accessionA0A1D5AG16
Subcellular Location
UniProt Annotation
GO Annotation
Phenotypes & Variants
Disruption phenotype
Leads to the accumulation of pyran intermediates devoid of the medium-chain fatty acyl moiety such as monascusone A.
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000460203 | 1-1842 | Fatty acid synthase alpha subunit pigJ | |||
Sequence: MAVRKLVPETAPVVDDAPASTSVDHKRSLAHKLLIELLSYQLALPVRWIETQNELLQWPETIQRYVEVGPRTTLVTMAKKTAARRASSQIVSASKLSTLKFLCTSDNTAEIYYEYPQESGAPVEEEGSKSDAAAPALAVSGSSRTATTAKATVTTPSSSSPETAPPAASTPSQGTPAGGSTTPDIPLSAKHVVLAMIAQKFRRAFDNIPTQKTVQELSGGKSTLQNEIMGDLAVEFGQLPDGGEYIPLDALGDALQGNFPGKPGKQMSSLITKLISRKMPGGFNQAAMQNHLEREWGFSKAHGQVVICLAITVEPESRLESADSAREFLDGLVSRYASYAGITMTPRGKGNVSADHSSAVMVDESVLNGIKREQRDYQIKELELLSKHLQLDTAADDAVLNELRASQKSLEEKLDRWASEFDDKFFSGIEAIFDARKVRQYDSWWNWAREDTMRLLSRMRPGQLPLQHLQEQGLVAQLLRRWEPSCAEIVQNFLDTGECKEPFLATAAEILRLGSDALKKSPVYRFTTPSMKPRTVISATGCVEYSEVPRENSSYIALLKQGLVAASGERVPYVHLKKKAPDQAWRYDAQSTEILLEALGTGSGAGLTFSGKTVLVTGAGPNSIGAAVVRGLLNGGAKVIVTTSRSVSSAASFFQRMYRECAARGATMAVVPFNQASKRDCESLVEYIYGAHSPVDGDLDYLVPFGAIPEKVELSKLDGASELAHRAMLVNILRILGLVYKEKEQRGLRTRPTTVIVPLSFNLGGFGGDGLYPESKIGLEALFNRYFSGNWSDYLSICGAAIGWVRGTTLSQSIRLLGEAIEHANGLDVITFSQEEMAFNILALMTPSIAETCEEGPVYADLTGGAKAIANIKDVMAAARAKFLKESSIQKALLAERAYEQRVLYGSESPRNDTSSPRPRLSTKRARLSLEFPEVPSKSDLKAHLVDLQGMVDLSRTVVVVGFSELGPWGNARTRWQMEHLTDLTPEGYIEMAWIMGLVEHFQGHLDGKPFVGWVDAQTKQPVADAEFKEKYQAHILAHAGLRFVEPDLLGGYDPSKKEFLQEIVVEEALPSFSTSKANADAFRLRLGDKVAVRRMPESDEYLVQVKRGAHFFVPKAVPFNRGVAGLLPAGWDPLRYGIPEDIVQQVDPVTLYALCCVSEALLSAGIRDPYELYRYIHVSELANCLGTGAGAQSAAQRLYKKRYLDHAVQSDILSESFLNTTAAWVNMLVFSSTGPIKTPVGACATAIESLDIGCDAIRSGRSQVALVGGYDDFREEASYEFAMMNATASSVGELAQGRLPREMSRPSTTTRGGFVESAGCGVQLIMNAELAIEMGLPIHAIIAYTQMAGDKIGRSIPAPGQGILTAARETSAGHDSALLDLAHRRKRLTDEVDAVHQWVTQQLAATRGPAGWPDRAIDEIEATALRKIKHAQHAWGNDIRCQDPSISPLKASLATWGLTIDDVQVVSMHGTSTKANDTNEADVISQQMDHLGRRPGNPLLAVCQKALTGHPKGAAGAWQLHGCMQMLQTGIVPGNRNADNIDSKLRQHRHIVYPMESMPMPQLKAAMLTSFGFGQKGGIAVVVAARHLFSAMAEDELEAYRRRVAKRQREADSAYVSGIMSKSLFKAKEVSVWGKSDASMSRMLLDPKARVGGHPENNNNNNNNSSSKRNTSIERLTRLLLPSQKPETEASPEGQQSTSLTASIQALLASQSTTRPTSTSIGVDVEAISSIPMGNAVFLERNFTRSERDHCFSSPTPQASFAGRWSAKEAVFKSLQTPSVGAGAAMAEIEIVSDGGVPKVQLHGRAKEVALAKGIRNIQASITHSGETVTAVALAESSPMC | ||||||
Modified residue | 222 | O-(pantetheine 4'-phosphoryl)serine | ||||
Sequence: S |
Keywords
- PTM
Expression
Induction
Expression does not seem to be regulated by the azaphilone pigments (MonAzPs) gene cluster-specific transcription regulator pigB.
Interaction
Subunit
[Alpha6beta6] hexamers of two multifunctional subunits (alpha and beta).
Structure
Family & Domains
Features
Showing features for region, compositional bias, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 120-184 | Disordered | ||||
Sequence: GAPVEEEGSKSDAAAPALAVSGSSRTATTAKATVTTPSSSSPETAPPAASTPSQGTPAGGSTTPD | ||||||
Compositional bias | 140-182 | Polar residues | ||||
Sequence: SGSSRTATTAKATVTTPSSSSPETAPPAASTPSQGTPAGGSTT | ||||||
Domain | 184-262 | Carrier | ||||
Sequence: DIPLSAKHVVLAMIAQKFRRAFDNIPTQKTVQELSGGKSTLQNEIMGDLAVEFGQLPDGGEYIPLDALGDALQGNFPGK | ||||||
Region | 611-807 | Beta-ketoacyl reductase | ||||
Sequence: GKTVLVTGAGPNSIGAAVVRGLLNGGAKVIVTTSRSVSSAASFFQRMYRECAARGATMAVVPFNQASKRDCESLVEYIYGAHSPVDGDLDYLVPFGAIPEKVELSKLDGASELAHRAMLVNILRILGLVYKEKEQRGLRTRPTTVIVPLSFNLGGFGGDGLYPESKIGLEALFNRYFSGNWSDYLSICGAAIGWVRG | ||||||
Domain | 1058-1585 | Ketosynthase family 3 (KS3) | ||||
Sequence: KEFLQEIVVEEALPSFSTSKANADAFRLRLGDKVAVRRMPESDEYLVQVKRGAHFFVPKAVPFNRGVAGLLPAGWDPLRYGIPEDIVQQVDPVTLYALCCVSEALLSAGIRDPYELYRYIHVSELANCLGTGAGAQSAAQRLYKKRYLDHAVQSDILSESFLNTTAAWVNMLVFSSTGPIKTPVGACATAIESLDIGCDAIRSGRSQVALVGGYDDFREEASYEFAMMNATASSVGELAQGRLPREMSRPSTTTRGGFVESAGCGVQLIMNAELAIEMGLPIHAIIAYTQMAGDKIGRSIPAPGQGILTAARETSAGHDSALLDLAHRRKRLTDEVDAVHQWVTQQLAATRGPAGWPDRAIDEIEATALRKIKHAQHAWGNDIRCQDPSISPLKASLATWGLTIDDVQVVSMHGTSTKANDTNEADVISQQMDHLGRRPGNPLLAVCQKALTGHPKGAAGAWQLHGCMQMLQTGIVPGNRNADNIDSKLRQHRHIVYPMESMPMPQLKAAMLTSFGFGQKGGIAVVVA | ||||||
Region | 1649-1672 | Disordered | ||||
Sequence: KARVGGHPENNNNNNNNSSSKRNT | ||||||
Compositional bias | 1655-1672 | Polar residues | ||||
Sequence: HPENNNNNNNNSSSKRNT |
Sequence similarities
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,842
- Mass (Da)199,882
- Last updated2016-11-30 v1
- ChecksumF1CFA1727F134240
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 140-182 | Polar residues | ||||
Sequence: SGSSRTATTAKATVTTPSSSSPETAPPAASTPSQGTPAGGSTT | ||||||
Compositional bias | 1655-1672 | Polar residues | ||||
Sequence: HPENNNNNNNNSSSKRNT |