ID   MACF_PENTR              Reviewed;         519 AA.
AC   A0A2P1DP98;
DT   23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT   23-MAY-2018, sequence version 1.
DT   03-AUG-2022, entry version 10.
DE   RecName: Full=FAD-dependent monooxygenase macF {ECO:0000303|PubMed:28926261};
DE            EC=1.-.-.- {ECO:0000250|UniProtKB:G3Y424};
DE   AltName: Full=Macrophorins biosynthesis cluster protein F {ECO:0000303|PubMed:28926261};
DE   Flags: Precursor;
GN   Name=macF {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: FAD-dependent 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:G3Y424,
CC       ECO:0000269|PubMed:28926261}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC       {ECO:0000269|PubMed:28926261}.
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 oxygen-dependent FAD-linked oxidoreductase
CC       family. {ECO:0000305}.
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DR   EMBL; MF990005; AVK70106.1; -; Genomic_DNA.
DR   EMBL; MH388470; QBC75442.1; -; Genomic_DNA.
DR   UniPathway; UPA00213; -.
DR   GO; GO:0071949; F:FAD binding; IEA:InterPro.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR   Gene3D; 3.30.465.10; -; 1.
DR   InterPro; IPR016166; FAD-bd_PCMH.
DR   InterPro; IPR036318; FAD-bd_PCMH-like_sf.
DR   InterPro; IPR016169; FAD-bd_PCMH_sub2.
DR   InterPro; IPR006094; Oxid_FAD_bind_N.
DR   Pfam; PF01565; FAD_binding_4; 1.
DR   SUPFAM; SSF56176; SSF56176; 1.
DR   PROSITE; PS51387; FAD_PCMH; 1.
PE   3: Inferred from homology;
KW   FAD; Flavoprotein; Oxidoreductase; Signal.
FT   SIGNAL          1..20
FT                   /evidence="ECO:0000255"
FT   CHAIN           21..519
FT                   /note="FAD-dependent monooxygenase macF"
FT                   /id="PRO_5015136411"
FT   DOMAIN          88..262
FT                   /note="FAD-binding PCMH-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00718"
FT   MOD_RES         125
FT                   /note="Pros-8alpha-FAD histidine"
FT                   /evidence="ECO:0000250|UniProtKB:P08159"
SQ   SEQUENCE   519 AA;  55144 MW;  3975E83101269FC5 CRC64;
     MTKMTSIIGI LMGVLTTATA ASIPTGSSAA AAAALGSLGV SPPSGNVLIG NAGYTCSLLN
     RVLSKNETFT VTSPYYDVLI DEAWSENCRL NASCIVTPES AEEVSRLLQI LSILETRFAI
     RSGGHNTNPG FSSIGSDGVL IALEKLDSIS LSADRGTVTV GPGNKWESVY KYLQPYNLTA
     LGGREAVVGV GGYILGETGG LSTFYNTHGL AIDSVTRFQV VLPNGTIVDA TPTEHADLYK
     GLKGGLNNFG IVTEYDLTTN TGVDIYYEIK TYTTANTPAV LAAYATYLLD ADINSNVEIQ
     INPSYTLVFY GYLGHVSAPT DFDPFSDIPV ASTMYPPTNG SLTELLLSIG STGLTSEGVS
     YSGTFSFKVT GSTFLQDTYS TYLEAAASLP TGAVLSYVPQ GVIPNLVTQG KSQNGGNLLG
     LDATPQVWAN IFVQFPATLS QSEVAGSVDS LLANLISSAK SEDLFLPYIF VNDAGAKQKP
     LQSFGEKNIK YIDTVAKRYD PKRIMQRLQN QAYFVLEEL