MILB_CORMM
ID MILB_CORMM Reviewed; 358 AA.
AC G3JUI7;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 1.
DT 03-AUG-2022, entry version 40.
DE RecName: Full=Trans-enoyl reductase milB {ECO:0000303|PubMed:34548637};
DE EC=1.-.-.- {ECO:0000303|PubMed:34548637};
DE AltName: Full=Cordypyrones biosynthesis cluster protein B {ECO:0000303|PubMed:34548637};
GN Name=milB {ECO:0000303|PubMed:34548637}; ORFNames=CCM_09345;
OS Cordyceps militaris (strain CM01) (Caterpillar fungus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Cordycipitaceae; Cordyceps.
OX NCBI_TaxID=983644;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CM01;
RX PubMed=22112802; DOI=10.1186/gb-2011-12-11-r116;
RA Zheng P., Xia Y., Xiao G., Xiong C., Hu X., Zhang S., Zheng H., Huang Y.,
RA Zhou Y., Wang S., Zhao G.-P., Liu X., St Leger R.J., Wang C.;
RT "Genome sequence of the insect pathogenic fungus Cordyceps militaris, a
RT valued traditional Chinese medicine.";
RL Genome Biol. 12:RESEARCH116.1-RESEARCH116.21(2011).
RN [2]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=34548637; DOI=10.1038/s41429-021-00478-3;
RA Gao Y.L., Yu C., Li L.;
RT "Heterologous expression of a natural product biosynthetic gene cluster
RT from Cordyceps militaris.";
RL J. Antibiot. 75:16-20(2022).
CC -!- FUNCTION: Trans-enoyl reductase; part of the gene cluster that mediates
CC the biosynthesis of cordypyrones A and B, 2 pyrones that show modest
CC activities against pathogenic bacteria including methicillin-resistant
CC Staphylococcus aureus (MRSA), Mycobacterium tuberculosis and Bacillus
CC cereus (PubMed:34548637). The HR-PKS milA catalyzes the formation of
CC cordypyrones A via condensation of one acetate with 10 malonate units
CC (PubMed:34548637). Since milA lacks an enoyl reductase domain, the 2
CC beta-keto processing domains DH and KR of milA collaborate with the
CC trans-enoyl reductase milB to catalyze the different levels of
CC reduction (PubMed:34548637). The cytochrome P450 monooxygenase milC
CC then hydroxylates the C-22 of cordypyrones A to yield cordypyrones B
CC (PubMed:34548637). {ECO:0000269|PubMed:34548637}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + 3 AH2 + 18 H(+) + 10 malonyl-CoA + 8 NADPH = 3 A
CC + 10 CO2 + 11 CoA + cordypyrone A + 8 H2O + 8 NADP(+);
CC Xref=Rhea:RHEA:71139, ChEBI:CHEBI:13193, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:17499,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57288, ChEBI:CHEBI:57384,
CC ChEBI:CHEBI:57783, ChEBI:CHEBI:58349, ChEBI:CHEBI:190187;
CC Evidence={ECO:0000269|PubMed:34548637};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:71140;
CC Evidence={ECO:0000269|PubMed:34548637};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:34548637}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q9Y7D0}.
CC -!- SIMILARITY: Belongs to the zinc-containing alcohol dehydrogenase
CC family. {ECO:0000305}.
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DR EMBL; JH126407; EGX87723.1; -; Genomic_DNA.
DR RefSeq; XP_006674542.1; XM_006674479.1.
DR STRING; 73501.XP_006674542.1; -.
DR EnsemblFungi; EGX87723; EGX87723; CCM_09345.
DR GeneID; 18171348; -.
DR KEGG; cmt:CCM_09345; -.
DR eggNOG; KOG1198; Eukaryota.
DR HOGENOM; CLU_026673_16_1_1; -.
DR InParanoid; G3JUI7; -.
DR OrthoDB; 913304at2759; -.
DR Proteomes; UP000001610; Unassembled WGS sequence.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:InterPro.
DR InterPro; IPR013149; ADH-like_C.
DR InterPro; IPR013154; ADH_N.
DR InterPro; IPR011032; GroES-like_sf.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR020843; PKS_ER.
DR Pfam; PF08240; ADH_N; 1.
DR Pfam; PF00107; ADH_zinc_N; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
PE 1: Evidence at protein level;
KW NADP; Nucleotide-binding; Oxidoreductase; Reference proteome.
FT CHAIN 1..358
FT /note="Trans-enoyl reductase milB"
FT /id="PRO_0000455746"
FT BINDING 48..51
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 170..173
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 193..196
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 211
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 258..259
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
FT BINDING 349..350
FT /ligand="NADP(+)"
FT /ligand_id="ChEBI:CHEBI:58349"
FT /evidence="ECO:0000250|UniProtKB:Q9Y7D0"
SQ SEQUENCE 358 AA; 38191 MW; E6273A35A0D7241A CRC64;
MTTVPTTQRA VVVGPEDGSV VVAESIPLPD IEPDAVLVQV SAVALNPVDT KMMPGFLNPG
NVLGLDFAGT VVAVGPAQPA WRSLQVGDRV FGCTDGCDSR RPRVGAFTQF TACRGSILIK
MPDHMSFATA ASMGNAIFSS GFALFHSLQL PGSLTATAEK SHWVLIYGGA TATGTMALQF
LRRAGHKPIA VCSAKHFDMA REYGAVAAFD YHSESHVQEI RDLTKNALSF AFDCVTTQSS
VLACEEAMGR LGGRYTALDP FDPTLVSRKA VKLDWILTLT LMGRGSVWPK PFGCEPDEAL
LTWGTKLAEV AEGVLAEGDH VLKAHPMRIM EGGLDAIPSG IDAIRQGQVR GFKLVYLL
