ID   MACD_PENTR              Reviewed;         330 AA.
AC   A0A2P1DP77;
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=Short chain dehydrogenase macD {ECO:0000303|PubMed:28926261};
DE            EC=1.1.1.- {ECO:0000250|UniProtKB:G3Y422};
DE   AltName: Full=Macrophorins biosynthesis cluster protein D {ECO:0000303|PubMed:28926261};
GN   Name=macD {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: Short chain dehydrogenase; 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:G3Y422,
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 short-chain dehydrogenases/reductases (SDR)
CC       family. {ECO:0000305}.
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DR   EMBL; MF990002; AVK70103.1; -; Genomic_DNA.
DR   EMBL; MH388470; QBC75445.1; -; Genomic_DNA.
DR   UniPathway; UPA00213; -.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR002347; SDR_fam.
DR   Pfam; PF00106; adh_short; 1.
DR   PRINTS; PR00081; GDHRDH.
DR   SUPFAM; SSF51735; SSF51735; 1.
PE   3: Inferred from homology;
KW   NAD; NADP; Oxidoreductase.
FT   CHAIN           1..330
FT                   /note="Short chain dehydrogenase macD"
FT                   /id="PRO_0000454088"
FT   ACT_SITE        204
FT                   /note="Proton acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
FT   BINDING         24..32
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
FT   BINDING         51..52
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
FT   BINDING         109..111
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
FT   BINDING         204..208
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
FT   BINDING         237..239
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250|UniProtKB:Q92506"
SQ   SEQUENCE   330 AA;  36328 MW;  0A84D2D0E861B287 CRC64;
     MVNIIQPKVD PLPTGIGLTG KTVVITGASA GMGLEATKQL LRLRASTVIL AVRNVAKGEA
     CATSLRQDRR IQTHNPKPTI KVMELDVDDY HSVQRFSKQL REEIPVVHIL ILNAGIGLLK
     LERSASGHDR TTQVNYYSNV LLIAELLPYL QAGAEKTGSP ARISWVGSRA HEVTSLEKKA
     PIKPGEGVLA HMDKEEAFVP FQRYGDSKLL CVMFMYNLAP RLDPKKVIIN MMCPGMVNTN
     MSDVLPMHLR LIVNVVKSFR ARPVEVGGWI ILNSALVVGP ESHGKFLNDK TISDKSAFIK
     SPAGQEIQKK LWEETINEIG TLTTLPAELK