CM3C_CORMM
ID CM3C_CORMM Reviewed; 637 AA.
AC G3J455;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 16-NOV-2011, sequence version 1.
DT 03-AUG-2022, entry version 34.
DE RecName: Full=Acyl-CoA ligase cm3C {ECO:0000303|PubMed:31926180};
DE EC=6.2.1.- {ECO:0000305|PubMed:31926180};
DE AltName: Full=Beauveriolides biosynthesis cluster protein C {ECO:0000303|PubMed:31926180};
DE AltName: Full=Cyclodepsipeptides cm3 biosynthesis cluster protein C {ECO:0000303|PubMed:31926180};
GN Name=cm3C {ECO:0000303|PubMed:31926180}; ORFNames=CCM_01284;
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 BIOTECHNOLOGY.
RX PubMed=14718664; DOI=10.1073/pnas.0307757100;
RA Namatame I., Tomoda H., Ishibashi S., Omura S.;
RT "Antiatherogenic activity of fungal beauveriolides, inhibitors of lipid
RT droplet accumulation in macrophages.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:737-742(2004).
RN [3]
RP BIOTECHNOLOGY.
RX PubMed=19396893; DOI=10.1002/cbic.200900139;
RA Witter D.P., Chen Y., Rogel J.K., Boldt G.E., Wentworth P. Jr.;
RT "The natural products beauveriolide I and III: a new class of beta-amyloid-
RT lowering compounds.";
RL ChemBioChem 10:1344-1347(2009).
RN [4]
RP BIOTECHNOLOGY.
RX PubMed=19336931; DOI=10.1248/cpb.57.377;
RA Ohshiro T., Matsuda D., Nagai K., Doi T., Sunazuka T., Takahashi T.,
RA Rudel L.L., Omura S., Tomoda H.;
RT "The selectivity of beauveriolide derivatives in inhibition toward the two
RT isozymes of acyl-CoA: cholesterol acyltransferase.";
RL Chem. Pharm. Bull. 57:377-381(2009).
RN [5]
RP FUNCTION, AND PATHWAY.
RX PubMed=31926180; DOI=10.1016/j.jbiotec.2020.01.002;
RA Wang X., Gao Y.L., Zhang M.L., Zhang H.D., Huang J.Z., Li L.;
RT "Genome mining and biosynthesis of the Acyl-CoA:cholesterol acyltransferase
RT inhibitor beauveriolide I and III in Cordyceps militaris.";
RL J. Biotechnol. 309:85-91(2020).
CC -!- FUNCTION: Acyl-CoA ligase; part of the gene cluster that mediates the
CC biosynthesis of beauveriolides I and III, cyclodepsipeptides acting as
CC inhibitors of the acyl-CoA:cholesterol acyltransferase
CC (PubMed:31926180). The HR-PKS cm3B initiates the biosynthesis of
CC beauveriolides by iteratively catalyzing the formation of the linear
CC polyketide chain (Probable). The ATP-dependent acetyl-CoA ligase cm3D
CC converts the polyketide carboxylic acid to a CoA thioester which id
CC shuttled to the first T domain in the NRPS cm3A by the
CC acetyltransferase cm3C (Probable). Cm3A contains 13 domains and
CC assembles the polyketide chain, L-phenylalanine, L-alanine, and D-
CC leucine (or D-allo-isoleucine) to form beauveriolide I (or
CC beauveriolide III). The production of both beauveriolides I and III
CC suggests the substrate adaptability of cm3B, using different amino
CC acids as substrates (Probable). {ECO:0000269|PubMed:31926180,
CC ECO:0000305|PubMed:31926180}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:31926180}.
CC -!- DOMAIN: Both substrate-binding domains (SBD1 and SBD2) are involved in
CC the substrate recognition, and are sufficient to confer the substrate
CC specificity. {ECO:0000250|UniProtKB:Q42524}.
CC -!- BIOTECHNOLOGY: Beauveriolides inhibit selectively the acyl-
CC CoA:cholesterol acyl-transferases (ACATs), leading to blocking the
CC synthesis of cholesteryl esters and decreasing the cholesterol
CC concentration, which suggests that beauveriolides are promising as
CC potential lead compounds for antiatherosclerotic agents
CC (PubMed:14718664, PubMed:19336931). Moreover, this activity correlates
CC with inhibitory activities of beauveriolides in the secretion of
CC amyloid-beta-peptide, which suggests that beauveriolides may be an
CC attractive new candidate for the treatment of Alzheimer's disease
CC (PubMed:19396893). {ECO:0000269|PubMed:14718664,
CC ECO:0000269|PubMed:19336931, ECO:0000269|PubMed:19396893}.
CC -!- SIMILARITY: Belongs to the ATP-dependent AMP-binding enzyme family.
CC {ECO:0000305}.
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DR EMBL; JH126399; EGX96626.1; -; Genomic_DNA.
DR RefSeq; XP_006666503.1; XM_006666440.1.
DR AlphaFoldDB; G3J455; -.
DR SMR; G3J455; -.
DR STRING; 73501.XP_006666503.1; -.
DR EnsemblFungi; EGX96626; EGX96626; CCM_01284.
DR GeneID; 18163315; -.
DR KEGG; cmt:CCM_01284; -.
DR eggNOG; KOG1176; Eukaryota.
DR HOGENOM; CLU_000022_59_2_1; -.
DR InParanoid; G3J455; -.
DR OMA; VTTHAMF; -.
DR OrthoDB; 683933at2759; -.
DR Proteomes; UP000001610; Unassembled WGS sequence.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR InterPro; IPR025110; AMP-bd_C.
DR InterPro; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF13193; AMP-binding_C; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Ligase; Nucleotide-binding; Reference proteome.
FT CHAIN 1..637
FT /note="Acyl-CoA ligase cm3C"
FT /id="PRO_0000449818"
FT REGION 353..423
FT /note="SBD1"
FT /evidence="ECO:0000250|UniProtKB:Q42524"
FT REGION 424..486
FT /note="SBD2"
FT /evidence="ECO:0000250|UniProtKB:Q42524"
FT BINDING 282..290
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q08AH3"
FT BINDING 423..428
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q08AH3"
FT BINDING 507
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q08AH3"
FT BINDING 526
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q08AH3"
FT BINDING 624
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:Q08AH3"
SQ SEQUENCE 637 AA; 69944 MW; 2CA7D992E77D8C2C CRC64;
MVGEPKIVSV WQFPFPIVTG RHLPYCPGNC AAHLNYEIAH QLLFSLSHQP RSRILVNRMI
FSSPAWVPSP DQSAPDQVPI GDYVLSNHVL SKNDAPFVDA ISGHVYTMAM LRTRVESLAR
GLAADLNWSP NTGSPEEKVV AIYSLNTVAL SGPLLTIMYK IDYFILCWAV HRLNGICMPL
HSTCTSAEIT SHMITASCTT IFTCSGLMST CLEAAKELQL PAEKIYTLAL PSTYLDNANL
EDSPRLKTLE QLADQGSQLP QLEPLRWSAG QGKSQVAFLC STSGTSGRQK LAMLTHYGII
TNLLQMSAFE GFANDTYGQT VAAAIPFSHS YGILIGHVGV LRGESHIVFP RFDMQRMLGS
VASYRVNRLY LVPPILAVLG ANSFLMEPFD LSSVTSVVTG AAALDRTVAG RLKSLQPSWE
FLHAWGLTET CIVVTFTSKH DVWYGSSGSL LPGCQLRLVD AEGKDVENYD QSGEVYYKAP
NMFVGYLGDH ESTISSFDDD GWMRTGDMGA IQVSPNGVEH LFIRDRIKDM IKVKGMQVIP
ADVEAAMLTH PAVADVAVIG VPDELAGERA MAFVIRSTSV MSEFSEDDLR DSINDHLEDR
LHETHWLGDR LEFVAEIPKS QSGKVLKKIL REKAASN
