CM3D_CORMM
ID CM3D_CORMM Reviewed; 485 AA.
AC G3J454;
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=Acyltransferase cm3D {ECO:0000303|PubMed:31926180};
DE EC=2.3.1.- {ECO:0000305|PubMed:31926180};
DE AltName: Full=Beauveriolides biosynthesis cluster protein D {ECO:0000303|PubMed:31926180};
DE AltName: Full=Cyclodepsipeptides cm3 biosynthesis cluster protein D {ECO:0000303|PubMed:31926180};
GN Name=cm3D {ECO:0000303|PubMed:31926180}; ORFNames=CCM_01283;
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: Acyltransferase; 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 -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q70PR7}.
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 plant acyltransferase family. {ECO:0000305}.
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DR EMBL; JH126399; EGX96625.1; -; Genomic_DNA.
DR RefSeq; XP_006666502.1; XM_006666439.1.
DR AlphaFoldDB; G3J454; -.
DR SMR; G3J454; -.
DR EnsemblFungi; EGX96625; EGX96625; CCM_01283.
DR GeneID; 18163314; -.
DR KEGG; cmt:CCM_01283; -.
DR eggNOG; ENOG502RS7Z; Eukaryota.
DR HOGENOM; CLU_026450_1_0_1; -.
DR InParanoid; G3J454; -.
DR OMA; WGKPESV; -.
DR OrthoDB; 1130893at2759; -.
DR Proteomes; UP000001610; Unassembled WGS sequence.
DR GO; GO:0016746; F:acyltransferase activity; IEA:UniProtKB-KW.
DR Gene3D; 3.30.559.10; -; 2.
DR InterPro; IPR023213; CAT-like_dom_sf.
PE 1: Evidence at protein level;
KW Acyltransferase; Reference proteome; Transferase.
FT CHAIN 1..485
FT /note="Acyltransferase cm3D"
FT /id="PRO_0000449819"
FT ACT_SITE 169
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q70PR7"
SQ SEQUENCE 485 AA; 52222 MW; 8A75774CA68CA37E CRC64;
MECTTVKLSV ALGEEVVQLS TLDQQAQRAY ANLLLVFKLS QNADADHVFS SLKRGLGAAL
TEVPDFASLV VPVPGSKKNE LQLRLGPDSG VPFKLVRQDA LASHLEKHSS GGTYAELARD
NFPLASVPTE LLFNQLPASE LACARGLPGL LAQASVVDGG LIMGLSWHHT VSDARGINTL
LSSWARHTKM WAGQGTIGSP SAAPEPTRDR WRLTCGPRDV HVSHFSDYQI NAAARTPLSP
AAAHLLDRPD TTNATAGLST WYFSKKALSS LRGELGRAAA DGSDAVQFTS GEAVSALVWK
HLSLARLLHQ QLAHETSLFA SRIDFRGRAK PAFADGYIGN INEPNARTRM RLAEVCAPSS
PASLVALAAA VREAIGAMDE KTMREFIGLV EGSSSVTDVY WDYNTFPGPD LVVTDMSGMD
TLRQEWGGDL GQPVCIRSGS REKGVAYFLP QDAQGGFEVQ LQCTAEDLGR LKDDSLFTKY
AEFRS
