ID MACC_PENTR Reviewed; 536 AA. AC A0A2P1DP94; DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot. DT 23-MAY-2018, sequence version 1. DT 22-FEB-2023, entry version 10. DE RecName: Full=Cytochrome P450 monooxygenase macC {ECO:0000303|PubMed:28926261}; DE EC=1.-.-.- {ECO:0000250|UniProtKB:G3Y416}; DE AltName: Full=Macrophorins biosynthesis cluster protein C {ECO:0000303|PubMed:28926261}; GN Name=macC {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:G3Y416, 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; MF989996; AVK70097.1; -; Genomic_DNA. DR EMBL; MH388470; QBC75451.1; -; Genomic_DNA. DR AlphaFoldDB; A0A2P1DP94; -. DR UniPathway; UPA00213; -. DR GO; GO:0016020; C:membrane; IEA:UniProtKB-SubCell. 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:1901336; P:lactone biosynthetic process; IEA:UniProt. DR GO; GO:0043386; P:mycotoxin biosynthetic process; IEA:UniProt. DR GO; GO:1901617; P:organic hydroxy compound biosynthetic process; IEA:UniProt. DR GO; GO:0030639; P:polyketide biosynthetic process; IEA:UniProt. DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway. DR Gene3D; 1.10.630.10; Cytochrome P450; 1. DR InterPro; IPR001128; Cyt_P450. DR InterPro; IPR002401; Cyt_P450_E_grp-I. DR InterPro; IPR036396; Cyt_P450_sf. DR PANTHER; PTHR46300:SF2; CYTOCHROME P450 MONOOXYGENASE ALNH-RELATED; 1. DR PANTHER; PTHR46300; P450, PUTATIVE (EUROFUNG)-RELATED-RELATED; 1. DR Pfam; PF00067; p450; 1. DR PRINTS; PR00463; EP450I. DR SUPFAM; SSF48264; Cytochrome P450; 1. PE 3: Inferred from homology; KW Heme; Iron; Membrane; Metal-binding; Monooxygenase; Oxidoreductase; KW Transmembrane; Transmembrane helix. FT CHAIN 1..536 FT /note="Cytochrome P450 monooxygenase macC" FT /id="PRO_0000454086" FT TRANSMEM 2..22 FT /note="Helical" FT /evidence="ECO:0000255" FT BINDING 448 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 536 AA; 61412 MW; C980E6537D1E4DA4 CRC64; MALLYITTAA LALLLLFLRA VFKSWRIQRK LPPGPPGLPL IGNIHQIPAV RAHQKFTEWA KVYGGLYTFR IGPATAAVIT DRGLVKELLD KRSALYSSRP VSYVGQNLIT GGDHLLLMDN NEMWRLFRKT VHQHFKASMC EKEHVKLLEA EHTQMMRDFL LYPEKHMLHT KRTTNSIIMS LLYGIRTPSW DTPHMRELYE IMEQWSKVME TGATPPVDIF PWLRWIPQRW LGNWVDRSVE VGSGMKALYG SFRRRAIEAR REAEQSSQSR ARTFIDHVLD LQEKANLTDN QVDFLGGVMM EGGSDTGSTM LLVMIQALVR YPEVQERARA ELDAVCGEGR SPTWADFSRL PYINMIVKET MRWRPVTPLS FPHALNQDDW VNGYLLPKGT TVFLNVWGLH HDESIFPNPE RFDPSHYEGR HNLASDYAAS PDYMQRDHFI YGAGRRLCPG IHLSERSMFI GAAKLLWCFQ FEPEMDESGR PVAIDTDPIT GYTEGFLVCP QAYKCKVSPR STARAETIMR EFAQAESEVL CQYATP //