ASTB_TALWO
ID ASTB_TALWO Reviewed; 498 AA.
AC A0A3S9NM20;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 08-MAY-2019, sequence version 1.
DT 03-AUG-2022, entry version 13.
DE RecName: Full=Cytochrome P450 monooxygenase astB {ECO:0000303|PubMed:30548032};
DE EC=1.-.-.- {ECO:0000269|PubMed:30548032};
DE AltName: Full=Asperterpenoid biosynthesis cluster protein B {ECO:0000303|PubMed:30548032};
GN Name=astB {ECO:0000303|PubMed:30548032};
GN Synonyms=aspB {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=4 O2 + preasperterpenoid A + 4 reduced [NADPH--hemoprotein
CC reductase] = asperterpenoid A + 5 H(+) + 5 H2O + 4 oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:66836, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:167511, ChEBI:CHEBI:167512;
CC Evidence={ECO:0000269|PubMed:30548032};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66837;
CC Evidence={ECO:0000269|PubMed:30548032};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=asperterpenoid A + 2 O2 + 2 reduced [NADPH--hemoprotein
CC reductase] = asperterpenoid B + 3 H(+) + 3 H2O + 2 oxidized [NADPH--
CC hemoprotein reductase]; Xref=Rhea:RHEA:66840, Rhea:RHEA-COMP:11964,
CC Rhea:RHEA-COMP:11965, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:15379, ChEBI:CHEBI:57618, ChEBI:CHEBI:58210,
CC ChEBI:CHEBI:167512, ChEBI:CHEBI:167513;
CC Evidence={ECO:0000269|PubMed:30548032};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66841;
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; AZQ56743.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A3S9NM20; -.
DR SMR; A0A3S9NM20; -.
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; IPR002403; Cyt_P450_E_grp-IV.
DR InterPro; IPR036396; Cyt_P450_sf.
DR Pfam; PF00067; p450; 1.
DR PRINTS; PR00465; EP450IV.
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..498
FT /note="Cytochrome P450 monooxygenase astB"
FT /id="PRO_0000452655"
FT TRANSMEM 7..27
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 425
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 237
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 248
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 346
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 498 AA; 57028 MW; 311C315A637D712D CRC64;
MIDSLSFTTM PVVLLVGLVL YQLLAFTYRL FFSPLAKFPG QKIAGMTHWY EFYHDVIRRG
QYTFHIRDMH KKYGPILRIN PYELHISDPS FYNEIYAVQN RRRDRWEWST RPGGFGGSVG
GTNPHELHRR RRAALNPFFS RANIRKLQHE IDQKAVQLVE RLEKETDRVI KVNHAFAALT
NDIVMQYSFG RDDNRAAHKD RAARALPMEM LSKISSVVAM FWQEKQSITE EVRQILNGTN
KAYKERPNRT IYHGILESKL PPEEKELNRL AEEAQITIGA GTLATAWVMS VGMYHLLAPG
SVSMLKTLRE ELQRAIPDPS EPIDLAALEK LPYLTGVVKE CLRLGNGTTT RLQRIAPDET
LIYTDPNTGK VWDIPPGTPV SLSSLHIHHD ETIFADPESF RPERWIENPD LERYLLTFSK
GSRQCLGIHL AYAEMYIVLA RVFRLYGRKE EGPSKGPSDK LGNLELFETE LRDTLCVADL
VVPAVWEGSQ GIRIKVTE
