YANH_ASPNA
ID YANH_ASPNA Reviewed; 517 AA.
AC G3Y420;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 39.
DE RecName: Full=Cytochrome P450 monooxygenase yanH {ECO:0000303|PubMed:24684908};
DE EC=1.-.-.- {ECO:0000305|PubMed:24684908};
DE AltName: Full=Yanuthone D biosynthesis cluster protein H {ECO:0000303|PubMed:24684908};
DE Flags: Precursor;
GN Name=yanH {ECO:0000303|PubMed:24684908}; ORFNames=ASPNIDRAFT_193092;
OS Aspergillus niger (strain ATCC 1015 / CBS 113.46 / FGSC A1144 / LSHB Ac4 /
OS NCTC 3858a / NRRL 328 / USDA 3528.7).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=380704;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 1015 / CBS 113.46 / FGSC A1144 / LSHB Ac4 / NCTC 3858a / NRRL
RC 328 / USDA 3528.7;
RX PubMed=21543515; DOI=10.1101/gr.112169.110;
RA Andersen M.R., Salazar M.P., Schaap P.J., van de Vondervoort P.J.I.,
RA Culley D., Thykaer J., Frisvad J.C., Nielsen K.F., Albang R., Albermann K.,
RA Berka R.M., Braus G.H., Braus-Stromeyer S.A., Corrochano L.M., Dai Z.,
RA van Dijck P.W.M., Hofmann G., Lasure L.L., Magnuson J.K., Menke H.,
RA Meijer M., Meijer S.L., Nielsen J.B., Nielsen M.L., van Ooyen A.J.J.,
RA Pel H.J., Poulsen L., Samson R.A., Stam H., Tsang A., van den Brink J.M.,
RA Atkins A., Aerts A., Shapiro H., Pangilinan J., Salamov A., Lou Y.,
RA Lindquist E., Lucas S., Grimwood J., Grigoriev I.V., Kubicek C.P.,
RA Martinez D., van Peij N.N.M.E., Roubos J.A., Nielsen J., Baker S.E.;
RT "Comparative genomics of citric-acid-producing Aspergillus niger ATCC 1015
RT versus enzyme-producing CBS 513.88.";
RL Genome Res. 21:885-897(2011).
RN [2]
RP BIOTECHNOLOGY.
RX PubMed=11031048; DOI=10.1021/jo0006831;
RA Bugni T.S., Abbanat D., Bernan V.S., Maiese W.M., Greenstein M.,
RA Van Wagoner R.M., Ireland C.M.;
RT "Yanuthones: novel metabolites from a marine isolate of Aspergillus
RT niger.";
RL J. Org. Chem. 65:7195-7200(2000).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=24684908; DOI=10.1016/j.chembiol.2014.01.013;
RA Holm D.K., Petersen L.M., Klitgaard A., Knudsen P.B., Jarczynska Z.D.,
RA Nielsen K.F., Gotfredsen C.H., Larsen T.O., Mortensen U.H.;
RT "Molecular and chemical characterization of the biosynthesis of the 6-MSA-
RT derived meroterpenoid yanuthone D in Aspergillus niger.";
RL Chem. Biol. 21:519-529(2014).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of yanuthone D, a fungal isoprenoid
CC epoxycyclohexenone that acts as an antibiotic against fungi and
CC bacteria (PubMed:24684908). The first step of the pathway is the
CC synthesis of 6-methylsalicylic acid (6-MSA) by the polyketide synthase
CC yanA (PubMed:24684908). 6-MSA is then converted to m-cresol by the
CC decarboxylase yanB (PubMed:24684908). The cytochrome P450 monooxygenase
CC yanC then catalyzes the oxidation of m-cresol to toluquinol
CC (PubMed:24684908). Epoxidation of toluquinol is then performed by the
CC short chain dehydrogenase yanD, with the help of yanE, and a further
CC prenylation by yanG leads to 7-deacetoxyyanuthone A (PubMed:24684908).
CC The next step is the hydroxylation of C-22 of 7-deacetoxyyanuthone A by
CC the cytochrome P450 monooxygenase yanH to yield 22-deacetylyanuthone A
CC (PubMed:24684908). O-Mevalon transferase yanI then attaches mevalon to
CC the hydroxyl group of 22-deacetylyanuthone A to produce yanuthone E
CC (PubMed:24684908). Finally, the FAD-dependent monooxygenase yanF
CC oxidizes the hydroxyl group at C15 of yanuthone E to form yanuthone D
CC (PubMed:24684908). Furthermore, several branching points in the pathway
CC lead to the production of yanuthones F and G from 7-deacetoxyyanuthone
CC A; yanuthones H and I from 22-deacetylyanuthone A; and yanuthone J from
CC yanuthone E (PubMed:24684908). {ECO:0000269|PubMed:24684908}.
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:24684908}.
CC -!- DISRUPTION PHENOTYPE: Loses the ability to produce yanuthone D, but
CC accumulates 7-deacetoxyyanuthone A as well as two C-1 oxidized
CC yanuthone derivatives called yanuthone F and yanuthone G
CC (PubMed:24684908). {ECO:0000269|PubMed:24684908}.
CC -!- BIOTECHNOLOGY: Yanuthone D is an antibiotic against C.albicans,
CC methicillin-resistant S.aureus (MRSA), and vancomycin-resistant
CC Enterococcus (PubMed:11031048). {ECO:0000269|PubMed:11031048}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; ACJE01000012; EHA22197.1; -; Genomic_DNA.
DR AlphaFoldDB; G3Y420; -.
DR SMR; G3Y420; -.
DR EnsemblFungi; EHA22197; EHA22197; ASPNIDRAFT_193092.
DR VEuPathDB; FungiDB:ASPNIDRAFT2_1158652; -.
DR HOGENOM; CLU_001570_14_4_1; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000009038; Unassembled WGS sequence.
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; Metal-binding; Monooxygenase; Oxidoreductase;
KW Reference proteome; Signal.
FT SIGNAL 1..23
FT /evidence="ECO:0000255"
FT CHAIN 24..517
FT /note="Cytochrome P450 monooxygenase yanH"
FT /evidence="ECO:0000255"
FT /id="PRO_0000436767"
FT BINDING 461
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 338
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
SQ SEQUENCE 517 AA; 58775 MW; 5D19000DBDD5D82E CRC64;
MALFSVLSNA LSELPVSIWL AAAATFAVYH AIRAVYLIFF SPLAIFPGSP WAALGEYWEA
YWNIGVRPGH KGQTLFKLEQ MHKRLGPALR MGPNEVHIYD PAFYHELYRP GSRYYKDPSM
HKVLGAPTST LAESDPVRHK QRKAPLEPLF SKKNILSLEN MLMEHVDHCC QRFDELYSQG
KPVSMEWALK SLAMDMVSQF AFGQSLNAIA DPEFKSLPVR VFQQYLPSLH VIKAFPFVRL
LSSLPLWIAR RISHSVEMGH ELEQFAARRI DEYIEAAAQG KTPNFPTVME RLLIPIPEKG
YEVPDKQGLR DEILTLISAG DDTTGIANTV TLFNIIHNRT IHDRLLAELK TVMPTPTSHA
QYIQLEQLPY LTAVIKEGLR YSSPAASRTP RLVPPGGVRL PDGRFIPAGT RVGMAIYHIH
YNEGLFENPH EFDPERWLQG PEITAKRAKF LVPFSRGSRS CLGINLAYME MYMAIAYIVR
RFDLELVGTT PEDMKWDDMV VPQFHGEFRA LTKRRVD
