ASTA_TALWO
ID ASTA_TALWO Reviewed; 493 AA.
AC A0A3Q9FEJ4;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 10-APR-2019, sequence version 1.
DT 03-AUG-2022, entry version 13.
DE RecName: Full=Cytochrome P450 monooxygenase astA {ECO:0000303|PubMed:30548032};
DE EC=1.-.-.- {ECO:0000269|PubMed:30548032};
DE AltName: Full=Asperterpenoid biosynthesis cluster protein A {ECO:0000303|PubMed:30548032};
GN Name=astA {ECO:0000303|PubMed:30548032};
GN Synonyms=aspA {ECO:0000303|PubMed:30548032};
OS Talaromyces wortmannii (Penicillium wortmannii).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Trichocomaceae; Talaromyces;
OC Talaromyces sect. Islandici.
OX NCBI_TaxID=28567;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, PATHWAY,
RP AND BIOTECHNOLOGY.
RC STRAIN=ATCC 26942 / CBS 387.67 / CCM F-175 / VKM F-2091;
RX PubMed=30548032; DOI=10.1039/c8ob02832j;
RA Huang J.H., Lv J.M., Wang Q.Z., Zou J., Lu Y.J., Wang Q.L., Chen D.N.,
RA Yao X.S., Gao H., Hu D.;
RT "Biosynthesis of an anti-tuberculosis sesterterpenoid asperterpenoid A.";
RL Org. Biomol. Chem. 17:248-251(2019).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of the asperterpenoids, sesterterpenes that
CC exhibit anti-tuberculosis activity (PubMed:30548032). The first step of
CC the pathway is performed by the sesterterpene synthase astC that
CC possesses both prenyl transferase and terpene cyclase activity,
CC converting isopentenyl diphosphate and dimethylallyl diphosphate into
CC geranylfarnesyl diphosphate (GFPP) and further converting GFPP into
CC preasperterpenoid A, respectively (PubMed:30548032). The cytochrome
CC P450 monooxygenase astB then dually oxidizes preasperterpenoid A to
CC produce asperterpenoid A along with a minor product, asperterpenoid B
CC (PubMed:30548032). Finally, the cytochrome P450 monooxygenase astA
CC converts asperterpenoid A into asperterpenoid C (PubMed:30548032).
CC {ECO:0000269|PubMed:30548032}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=asperterpenoid A + O2 + reduced [NADPH--hemoprotein reductase]
CC = asperterpenoid C + H(+) + H2O + oxidized [NADPH--hemoprotein
CC reductase]; Xref=Rhea:RHEA:66844, Rhea:RHEA-COMP:11964, Rhea:RHEA-
CC COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC ChEBI:CHEBI:57618, ChEBI:CHEBI:58210, ChEBI:CHEBI:167512,
CC ChEBI:CHEBI:167514; Evidence={ECO:0000269|PubMed:30548032};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66845;
CC Evidence={ECO:0000269|PubMed:30548032};
CC -!- COFACTOR:
CC Name=heme; Xref=ChEBI:CHEBI:30413;
CC Evidence={ECO:0000250|UniProtKB:P04798};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:30548032}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- BIOTECHNOLOGY: Asperterpenoids A and B, but not the final product
CC asperterpenoid C, exhibit potent inhibitory activity against
CC Mycobacterium tuberculosis protein tyrosine phosphatase B with IC(50)
CC values of 3 to 6 uM. {ECO:0000269|PubMed:30548032}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; MK140602; AZQ56742.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A3Q9FEJ4; -.
DR SMR; A0A3Q9FEJ4; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0020037; F:heme binding; IEA:InterPro.
DR GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR GO; GO:0004497; F:monooxygenase activity; IEA:UniProtKB-KW.
DR GO; GO:0016705; F:oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen; IEA:InterPro.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 1.10.630.10; -; 1.
DR InterPro; IPR001128; Cyt_P450.
DR InterPro; IPR017972; Cyt_P450_CS.
DR InterPro; IPR002401; Cyt_P450_E_grp-I.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00463; EP450I.
DR PRINTS; PR00385; P450.
DR SUPFAM; SSF48264; SSF48264; 1.
DR PROSITE; PS00086; CYTOCHROME_P450; 1.
PE 1: Evidence at protein level;
KW Glycoprotein; Heme; Iron; Membrane; Metal-binding; Monooxygenase;
KW Oxidoreductase; Transmembrane; Transmembrane helix.
FT CHAIN 1..493
FT /note="Cytochrome P450 monooxygenase astA"
FT /id="PRO_0000452654"
FT TRANSMEM 5..25
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 433
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /ligand_part="Fe"
FT /ligand_part_id="ChEBI:CHEBI:18248"
FT /note="axial binding residue"
FT /evidence="ECO:0000250|UniProtKB:P04798"
FT CARBOHYD 174
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 286
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 493 AA; 56874 MW; 428A3607826C0B68 CRC64;
MEQREIILLG LAALAVTYQV IVWIYNAWFH PLSGYPGPKL FGASYLPGLY HRIRGDYVLV
HTALHERFGE VIRVSPNELS YINPQAWKDI TGQGSGRQDM EKDPLSFGRP MPNAPSIFNA
HRMDHSRIRR TMSHAFSASA LRRQESLIQS HVKMMIQCLR EHNEEVVDMV SWYNFTTFDM
FGDLAFGESF GCLTNSLYHP WVKMLIMSMK AGYFIIQAQK YPIFEKVLMS FIPRMMRQRR
RDHLALTQAK LAKRMAKPEE RPDFLSFILR HQDEATGMSL PELEINASTL IVAGSETTAT
LLSGCTYYLL RNPRVMEKLL NEVRTTFKSE DEIDITTVNG LKYMLAVLDE ALRVYPPAPG
NFHRLVPKEG SVICEKFVPG ETQVSVCHYA AYHSPCNFHQ PDEFIPERFL GESKFENDRR
DVLQPFGTGS RACLGRNLAY FEMRLILTHV LWNFDLELMP QSKYWANQKV FAIWDKPELY
VKLKPRAGLE VRA
