MACH_PENTR
ID MACH_PENTR Reviewed; 510 AA.
AC A0A2P1DPA5;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 23-MAY-2018, sequence version 1.
DT 03-AUG-2022, entry version 9.
DE RecName: Full=Cytochrome P450 monooxygenase macH {ECO:0000303|PubMed:28926261};
DE EC=1.-.-.- {ECO:0000250|UniProtKB:G3Y420};
DE AltName: Full=Macrophorins biosynthesis cluster protein H {ECO:0000303|PubMed:28926261};
GN Name=macH {ECO:0000303|PubMed:28926261};
OS Penicillium terrestre.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=374132;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND PATHWAY.
RC STRAIN=LM2;
RX PubMed=28926261; DOI=10.1021/acs.orglett.7b02653;
RA Tang M.C., Cui X., He X., Ding Z., Zhu T., Tang Y., Li D.;
RT "Late-stage terpene cyclization by an integral membrane cyclase in the
RT biosynthesis of isoprenoid epoxycyclohexenone natural products.";
RL Org. Lett. 19:5376-5379(2017).
CC -!- FUNCTION: Cytochrome P450 monooxygenase; part of the gene cluster that
CC mediates the biosynthesis of macrophorins, isoprenoid
CC epoxycyclohexenones containing cyclized drimane moieties
CC (PubMed:28926261). The first step of the pathway is the synthesis of 6-
CC methylsalicylic acid (6-MSA) by the polyketide synthase macA
CC (PubMed:28926261). 6-MSA is then converted to m-cresol by the
CC decarboxylase macB (By similarity). The cytochrome P450 monooxygenase
CC macC then catalyzes the oxidation of m-cresol to toluquinol (By
CC similarity). Epoxidation of toluquinol is then performed by the short
CC chain dehydrogenase macD, with the help of macE, and a further
CC prenylation by macG leads to 7-deacetoxyyanuthone A (By similarity).
CC The next step is the hydroxylation of C-22 of 7-deacetoxyyanuthone A by
CC the cytochrome P450 monooxygenase macH to yield 22-deacetylyanuthone A
CC (By similarity). O-Mevalon transferase macI then attaches mevalon to
CC the hydroxyl group of 22-deacetylyanuthone A to produce yanuthone E (By
CC similarity). The terpene cyclase macJ catalyzes the cyclization of 22-
CC deacetylyanuthone A to macrophorin A (PubMed:28926261). MacJ is also
CC able to catalyze cyclization of yanuthone E and 7-deacetoxyyanuthone A
CC to their corresponding macrophorins (PubMed:28926261). The macJ
CC products can be further modified by macH and macJ, as well as by the
CC FAD-dependent monooxygenase macF, to produce additional macrophorins,
CC including 4'-oxomacrophorin A, 4'-oxomacrophorin D and 4'-
CC oxomacrophorin E (PubMed:28926261). {ECO:0000250|UniProtKB:G3Y420,
CC ECO:0000269|PubMed:28926261}.
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:28926261}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000255}; Single-pass membrane
CC protein {ECO:0000255}.
CC -!- MISCELLANEOUS: The macrophorins cluster contains a single gene
CC insertion (encoding for the terpene cyclase macJ) compared with the
CC yanuthone cluster that produces the linear compound yanuthone.
CC {ECO:0000269|PubMed:28926261}.
CC -!- SIMILARITY: Belongs to the cytochrome P450 family. {ECO:0000305}.
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DR EMBL; MF990000; AVK70101.1; -; Genomic_DNA.
DR EMBL; MH388470; QBC75447.1; -; Genomic_DNA.
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 3: Inferred from homology;
KW Heme; Iron; Membrane; Metal-binding; Monooxygenase; Oxidoreductase;
KW Transmembrane; Transmembrane helix.
FT CHAIN 1..510
FT /note="Cytochrome P450 monooxygenase macH"
FT /id="PRO_0000454087"
FT TRANSMEM 7..29
FT /note="Helical"
FT /evidence="ECO:0000255"
FT BINDING 454
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"
SQ SEQUENCE 510 AA; 57817 MW; F0E2C7F16A591A32 CRC64;
MALLSVLPVS LWLIAAGTFA VYHAIRAVYL IFFSPLAVFP GSPWAALGEY WEAYWNIGVK
PGRKGQMLFK LEEMHKRLGP ALRMGPNEVH IYDPAFYHEL YRPGSRYYKD PSMHKVLGAP
SSTLAESDPV RHKQRKAPLE PLFSKKNILS LEPMLMEHVD RCSQRFDELF AQGKPVSMEW
ALKSLAMDMV SQFAFGQSLN ALADPEFKSL PVRVFQQYLP SLHVIKAFPF VRLLNSLPLW
IAKRISHSVE MGHELEQFAA RRIDEYMAAA AAGKTPTFPT LMERLLIPIP EKGYAVPDKQ
GLRDELLTVI SAGDDTTGIA NTVTLFNIFN NREVHDRLLA ELKTVMPTPN SHVSYLQLEA
LPYLTAVIKE GLRYSSPAAS RTPRLVPPGG VRLPDGRFIP AGTRVGMAIY HIHYNETLFE
SPRVFDPERW LQGPEVTAER AKFLVPFSRG SRSCLGINLA YMEMYMAIAY IVRRFDLDLV
GTTEEDMKWD DMVVPQFHGE FMALTKRRED
