RDC1_METCM
ID RDC1_METCM Reviewed; 2090 AA.
AC B3FWT6;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2008, sequence version 1.
DT 03-AUG-2022, entry version 59.
DE RecName: Full=Non-reducing polyketide synthase rdc1 {ECO:0000303|PubMed:18567690};
DE Short=NR-PKS rdc1 {ECO:0000303|PubMed:18567690};
DE EC=2.3.1.- {ECO:0000305|PubMed:18567690};
DE AltName: Full=Radicicol biosynthesis cluster protein rdc1 {ECO:0000303|PubMed:18567690};
GN Name=rdc1 {ECO:0000303|PubMed:18567690};
OS Metacordyceps chlamydosporia (Nematophagous fungus) (Pochonia
OS chlamydosporia).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Clavicipitaceae; Pochonia.
OX NCBI_TaxID=280754;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RC STRAIN=ATCC 16683;
RX PubMed=18567690; DOI=10.1128/aem.00478-08;
RA Reeves C.D., Hu Z., Reid R., Kealey J.T.;
RT "Genes for the biosynthesis of the fungal polyketides hypothemycin from
RT Hypomyces subiculosus and radicicol from Pochonia chlamydosporia.";
RL Appl. Environ. Microbiol. 74:5121-5129(2008).
RN [2]
RP REVIEW ON BIOTECHNOLOGY.
RX PubMed=19860733; DOI=10.2174/156802609789895665;
RA Winssinger N., Fontaine J.G., Barluenga S.;
RT "Hsp90 inhibition with resorcyclic acid lactones (RALs).";
RL Curr. Top. Med. Chem. 9:1419-1435(2009).
CC -!- FUNCTION: Non-reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of radicicol, a resorcylic acid lactone
CC (RAL) that irreversibly inhibits the HSP90 molecular chaperone, an
CC important target for cancer chemotherapy (PubMed:18567690). The cluster
CC encodes only two apparent post-PKS enzymes, a cytochrome P450
CC monooxygenase (rdc4) and a non-heme halogenase (rdc2) that could
CC introduce the epoxide and the chlorine, respectively (PubMed:18567690).
CC If this cluster includes all the genes required for radicicol
CC biosynthesis, the remaining structural features of radicicol are
CC presumably generated by the PKSs rdc1 and rdc5 (PubMed:18567690). The
CC C-2' ketone could arise if the R-PKS rdc5 and NR-PKS rdc1 each carry
CC out four iterations, in contrast to the five iteration-three iteration
CC split for the hypothemycin PKSs (PubMed:18567690). The origin of the
CC cis 5',6' double bond is not known (PubMed:18567690). The radicicol R-
CC PKS rdc5 ER domain may catalyze either double bond isomerization or
CC reduction in the third iteration (PubMed:18567690).
CC {ECO:0000269|PubMed:18567690}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:18567690}.
CC -!- DOMAIN: Multidomain protein; including a starter unit:ACP transacylase
CC (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes
CC repeated decarboxylative condensation to elongate the polyketide
CC backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and
CC transfers the extender unit malonyl-CoA; a product template (PT) domain
CC that controls the immediate cyclization regioselectivity of the
CC reactive polyketide backbone; and an acyl-carrier protein (ACP) that
CC serves as the tether of the growing and completed polyketide via its
CC phosphopantetheinyl arm (By similarity).
CC {ECO:0000250|UniProtKB:Q5B0D0}.
CC -!- DOMAIN: The release of the polyketide chain from the non-reducing
CC polyketide synthase is mediated by the thioesterase (TE) domain
CC localized at the C-ter of the protein (By similarity).
CC {ECO:0000250|UniProtKB:Q5ATJ7}.
CC -!- BIOTECHNOLOGY: Radicicol is an important pharmacophore as an inhibitor
CC of heat shock protein 90 (Hsp90), an ATP-dependent chaperone involved
CC in the post-translational maturation and stabilization of over one
CC hundred proteins, and which activity has been implicated in diverse
CC pathologies ranging from oncology to neurodegenerative and infectious
CC diseases (PubMed:19860733).
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DR EMBL; EU520419; ACD39770.1; -; Genomic_DNA.
DR AlphaFoldDB; B3FWT6; -.
DR SMR; B3FWT6; -.
DR PRIDE; B3FWT6; -.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR018201; Ketoacyl_synth_AS.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR030918; PT_fungal_PKS.
DR InterPro; IPR032088; SAT.
DR InterPro; IPR001031; Thioesterase.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF14765; PS-DH; 1.
DR Pfam; PF16073; SAT; 1.
DR Pfam; PF00975; Thioesterase; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53474; SSF53474; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR TIGRFAMs; TIGR04532; PT_fungal_PKS; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Multifunctional enzyme; Phosphopantetheine;
KW Phosphoprotein; Transferase.
FT CHAIN 1..2090
FT /note="Non-reducing polyketide synthase rdc1"
FT /id="PRO_0000437586"
FT DOMAIN 1649..1726
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 12..250
FT /note="N-terminal acylcarrier protein transacylase (SAT)
FT domain"
FT /evidence="ECO:0000255"
FT REGION 378..811
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 912..1195
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 1304..1604
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255"
FT REGION 1615..1650
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1820..1964
FT /note="Thioesterase (TE) domain"
FT /evidence="ECO:0000255"
FT COMPBIAS 1636..1650
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 551
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 1003
FT /note="For acyl/malonyl transferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 1686
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2090 AA; 228569 MW; C0FDD4F128527B6F CRC64;
MKSHTSAAKV VFLVGDQVDS WHNGLQHVIK AAGATPWLQS YLDDLSNAIK AEIAEAALDN
ALHASLGTFS SLLELGERYR HRSDDLGMAQ CLLLHAVRSS LFLQMAKQSA HILSPESQTE
WLGISGGLIS LSPRFVAEDF ETLREASIEI GRLFVRLCKL VSVRSRAIED NTGVWGWAIL
GVSKDEIRKG LDKFQQNMRI PAIKRAQVGV TGPGWSTIIG PPSVLDLCIK QCPAIATATK
NPLNIHALQH TLAITQTDLN YIVGNSQLMS RALHHIRPRL WGMDDPEATY QNWGDMLRAI
CSQVLSLSLD IPEAVANLGA SLRGCDSVQI IQMDNTSHGP FVSTALKAPG RKATLLETHS
YLQTQFQGTE PPQKTGRIAI VGMSGRGPRS DNIDEFWDVI MQKQDTCTEV PKDRFDIDEF
YCEEHGKGNK ICTMTTKYGC FMDKPGHFDA RFFHISPRES MLMDPGHRHF LMSSYEALEM
AGYSDGPTKL TDPNRIAAFY GQVTDDWHDQ SHPTLGCDAY TLQGVQRAFS SGRLAWQFKW
EGPTYSLDSA CASTTAAIHL ACMSLLSNDI DMAVAGASNI LNYPHSFACL SKSGVLSDTG
NCKPYRDDAD GYCRADFVGS VVLKRLEDAV ADNDNILAVI ASSGRNHSGN STSITSSDPG
AQERLFRKVL RNANVSPDDI SYVEMHGTGT PVGDPAEMSA VGNVFKHRRR ADGPLPVGAV
KANFGHSEGA AGMASLLKCI MMFKTDTIPP QAGMPHALNP NFPPLSELNV EIPAEPKEFK
KTRSGEPRRI LLNNFDAAGG NACLLLEDWD GSHSPVAQLE DTTDTRSSHV VTLSSRTQAA
HKANKQNFLN WLRENTTARL ADIAYTTAAR RMHHPIRSAY TASTTEELMA RVEASIQVSE
SSSLTSQQTP IIFVFSGQGS HYAGMGSDLY QTSPSFRETV DLCGHIGKIH GFPPFIDLIA
DKAIDMSTKS TVQTQLAVLT LEIGLAAFWK AAGVQPSAVM GHSLGEYAAL HVSGVLSLAD
VLYLVGQRAS LLLERCEENG FAMLAVAMSA KETQELLDSN KEFPSCSIAC FNGPNATVIS
GEAHDISQLQ GRVSKASKVL PVPYGFHSFQ MDSIISEYST LADGVTFSEP KIPVASTLVG
SMIETKDIIN SVYLAQQTRQ PVDFIGGLNA IQQMFNDPIW LEIGPNQVCT QFVRASSSSS
SPNTKTLSTL EGQSRDWVAI NKCMAMLYTQ GIAIDWLALH KPFMNSLRMV TLPAYAWDTK
DYWITYAEAK AVQGTTSSAP RDIKQPIIST FAQHVAKESS SNAGKLEITF RASVADQNLQ
AVMEGHRMEQ LPICPGSGFC EAAFSAAAYV LESIGRKEDA TVTKMRLQHP VMHRPLTKNL
VGPDGELFTT ITMESKDSNN IHVSWKASAS GPKSSMFEMG TCTLVVQKNV KALQATWDRT
AYLVRDRMDS IIKSAEDGQG HWLKHDIFYS LFATTVQYDP LYKCTKMAYI SNDFSEAVAE
VVLQDNPADA KFMASPYWGE GIVHIAGFVV NANPLRSPGT CFINSGFESF EQTVEFRAGK
SYLAYARAHQ VEEGRKICQV FVFDSEGKIV AQCYNLSFVR ISNALLQHNL SEGASKPVGR
GMAKQEKQEV PATTEVVRQP EKEESRHSVD TPSFSDVLIN TIVSETGLDP SELTDDTVVA
ELGVDSIMSI EIANKVSNAT GEQLTPMFLH EYPTIGDIKR AFDILTPVSS ESDAELTEEY
DLLEDTVTEE AVVHVPSPSS TSLEAVVTGS ITTKQRDAPQ QPRSIGDGPE PAVRFTLLHG
RASKRVQDQQ ASPSPFYLIA DGTGSIATYL HLPPHINTKM TIYGVDSPYL HCPSRLTPDV
GIPGIAKLIV DELVKRQPQG VPFWLGGFSG GAMIAYEIAR QLSALGHVID SLLLIDMCPP
RQIQAQRYDD ELGLAMFDAI SGNDDSGVWE SSDKTHQHLK ALFASVSAYN PPPLAKGESP
PAKRVALIWA QKGMIDRCAN SPRFRQILAD RGLVTESYPG FMEDPKLGPV AWSLIHKTES
DLGPNGWDKF VGRDELLCMA VEADHLELPT PEFVHLLGEK MDMAFEHFGR
