ASTC_TALWO
ID ASTC_TALWO Reviewed; 754 AA.
AC A0A3Q9FFM1;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 10-APR-2019, sequence version 1.
DT 03-AUG-2022, entry version 16.
DE RecName: Full=Bifunctional sesterterpene synthase astC {ECO:0000303|PubMed:30548032};
DE EC=4.2.3.- {ECO:0000269|PubMed:30548032};
DE AltName: Full=Asperterpenoid biosynthesis cluster protein C {ECO:0000303|PubMed:30548032};
DE Flags: Precursor;
GN Name=astC {ECO:0000303|PubMed:30548032};
GN Synonyms=aspC {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: Bifunctional sesterterpene synthase; part of the gene cluster
CC that mediates the biosynthesis of the asperterpenoids, sesterterpenes
CC that exhibit anti-tuberculosis activity (PubMed:30548032). The first
CC step of the pathway is performed by the sesterterpene synthase astC
CC that 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=(2E,6E,10E,14E)-geranylfarnesyl diphosphate = diphosphate +
CC preasperterpenoid A; Xref=Rhea:RHEA:66832, ChEBI:CHEBI:33019,
CC ChEBI:CHEBI:57907, ChEBI:CHEBI:167511;
CC Evidence={ECO:0000269|PubMed:30548032};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:66833;
CC Evidence={ECO:0000269|PubMed:30548032};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:Q12051,
CC ECO:0000250|UniProtKB:Q40577};
CC Note=Binds 4 Mg(2+) ions per subunit. {ECO:0000250|UniProtKB:Q12051,
CC ECO:0000250|UniProtKB:Q40577};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:30548032}.
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: In the N-terminal section; belongs to the terpene synthase
CC family. {ECO:0000305}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the FPP/GGPP synthase
CC family. {ECO:0000305}.
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DR EMBL; MK140602; AZQ56744.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A3Q9FFM1; -.
DR SMR; A0A3Q9FFM1; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0016829; F:lyase activity; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR CDD; cd00685; Trans_IPPS_HT; 1.
DR Gene3D; 1.10.600.10; -; 2.
DR InterPro; IPR008949; Isoprenoid_synthase_dom_sf.
DR InterPro; IPR000092; Polyprenyl_synt.
DR InterPro; IPR033749; Polyprenyl_synt_CS.
DR Pfam; PF00348; polyprenyl_synt; 1.
DR SUPFAM; SSF48576; SSF48576; 2.
DR PROSITE; PS00723; POLYPRENYL_SYNTHASE_1; 1.
DR PROSITE; PS00444; POLYPRENYL_SYNTHASE_2; 1.
PE 1: Evidence at protein level;
KW Isoprene biosynthesis; Lyase; Magnesium; Metal-binding;
KW Multifunctional enzyme; Signal; Transferase.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..754
FT /note="Bifunctional sesterterpene synthase astC"
FT /id="PRO_5018734944"
FT REGION 58..388
FT /note="Sesterterpene synthase"
FT /evidence="ECO:0000250|UniProtKB:A1C8C3"
FT REGION 389..753
FT /note="Geranylfarnesyl diphosphate synthase"
FT /evidence="ECO:0000250|UniProtKB:A1C8C3"
FT REGION 392..414
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 392..407
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 149
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q40577"
FT BINDING 149
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q40577"
FT BINDING 153
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:Q40577"
FT BINDING 153
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:Q40577"
FT BINDING 512
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 512
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 516
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="3"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
FT BINDING 516
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="4"
FT /evidence="ECO:0000250|UniProtKB:Q12051"
SQ SEQUENCE 754 AA; 86033 MW; 3398FE73E7B9D0CD CRC64;
MASLEVFVLY LRIFFISFMS RARSLFSFVT SPAITAEHGK VQKLQAKPGS DRAPDSWIQY
RHSKLVDPST YNDLGLCGGL PLRVHKHAHL ADKGARRAQE DWKRLVGPIR NFTGCLSPRF
NGIAVAIPEC IPERLEAVTY ANEFAFLHDD ILDTVGKEDG EEENNEMARG FESVLEPSRN
VKMSVSGKSQ MQAKLILELL DLDESQAMVL LKSWEGLVKG ESGSQHFDFQ SLDEYLPHRV
VNLGQTFWFG IITFAMGLTV SNEEMELTKP ITEPAYATLA LANDFFSWEK EYVEFQGNPT
SGNMANAVWI IMKEHSVDLE EAKVICQDKI RESCEEYRRR KREFELQSAE QVSIDAHRYL
SALEFSISGN VVWSQYTERY HFHKPEHWRQ VENVDDDGNK SDDSGIAMKD SPESTVVDVE
DNVPSTFLNF GSSGTNIRSK KTLVSPVLET KLPEMTNQVV LAPFQYVSSL PSKKVRHHAI
DALNIWFSVP EADLNMIKDA IDQLHNASLM LDDIEDNSPL RRGHPSTHMI YGISQTINSA
NNLFVMSLDT IRQLKSPDCL DVFISELKRL HIGQSLDLFW TSNVQCPTLE EYYKMVDYKT
GGLFQMVAKL MGAKSPKSKR KVPDVSTLTT LFGRYFQIRD DYQNLMSKEY TDQKGFCEDL
DEGKFSLPLI HCLTTSPNIR LQSILHQRKT MGKMSFETKK LVLDHLEETK SLEYTKEMLD
CLHVRLHKEL DVLEKQTGVN NFLLRLLLKR LHVK
