RDC5_METCM
ID RDC5_METCM Reviewed; 2383 AA.
AC B3FWU0;
DT 02-NOV-2016, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2008, sequence version 1.
DT 03-AUG-2022, entry version 69.
DE RecName: Full=Reducing polyketide synthase rdc5 {ECO:0000303|PubMed:18567690};
DE Short=R-PKS rdc5 {ECO:0000303|PubMed:18567690};
DE EC=2.3.1.- {ECO:0000305|PubMed:18567690};
DE AltName: Full=Hypothemycin biosynthesis cluster protein rdc5 {ECO:0000303|PubMed:18567690};
GN Name=rdc5 {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: Reducing polyketide synthase; part of the gene cluster that
CC mediates the biosynthesis of radicicol, a resorcylic acid lactone (RAL)
CC that irreversibly inhibits the HSP90 molecular chaperone, an important
CC target for cancer chemotherapy (PubMed:18567690). The cluster encodes
CC only two apparent post-PKS enzymes, a cytochrome P450 monooxygenase
CC (rdc4) and a non-heme halogenase (rdc2) that could introduce the
CC epoxide and the chlorine, respectively (PubMed:18567690). If this
CC cluster includes all the genes required for radicicol biosynthesis, the
CC remaining structural features of radicicol are presumably generated by
CC the PKSs rdc1 and rdc5 (PubMed:18567690). The C-2' ketone could arise
CC if the R-PKS rdc5 and NR-PKS rdc1 each carry out four iterations, in
CC contrast to the five iteration-three iteration split for the
CC hypothemycin PKSs (PubMed:18567690). The origin of the cis 5',6' double
CC bond is not known (PubMed:18567690). The radicicol R-PKS rdc5 ER domain
CC may catalyze either double bond isomerization or reduction in the third
CC iteration (PubMed:18567690). {ECO:0000269|PubMed:18567690}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:18567690}.
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; ACD39774.1; -; Genomic_DNA.
DR AlphaFoldDB; B3FWU0; -.
DR SMR; B3FWU0; -.
DR GO; GO:0016746; F:acyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0009058; P:biosynthetic process; IEA:UniProt.
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 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; IPR011032; GroES-like_sf.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR020843; PKS_ER.
DR InterPro; IPR013968; PKS_KR.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR002364; Quin_OxRdtase/zeta-crystal_CS.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF16197; KAsynt_C_assoc; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF08659; KR; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF14765; PS-DH; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 2.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
DR PROSITE; PS01162; QOR_ZETA_CRYSTAL; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Multifunctional enzyme; NADP; Oxidoreductase;
KW Phosphopantetheine; Phosphoprotein; Transferase.
FT CHAIN 1..2383
FT /note="Reducing polyketide synthase rdc5"
FT /id="PRO_0000437587"
FT DOMAIN 2300..2377
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 13..441
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 550..881
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 932..1250
FT /note="Dehydrogenase (DH) domain"
FT /evidence="ECO:0000255"
FT REGION 1663..1977
FT /note="Enoyl reductase (ER) domain"
FT /evidence="ECO:0000255"
FT REGION 2002..2182
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255"
FT ACT_SITE 1776
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00590"
FT MOD_RES 2337
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2383 AA; 260150 MW; 72A54A6CC5919D2F CRC64;
MPSATAQDAR APIAIIGMSC RFPGDAEDPL KFWDLLKEGR EAYSEKTHRY NEEAFYHPGG
QFNNKRQNVL PVKGGYMLKQ DPYVFDAAFF NITAAEAISF DPKQRIAMEV TYEAFENAGM
TLQKAAGTRT ACYIGTSMSD YRDSIVRDFG NYPKYHLLGT SDEMISNRIS HFFDLRGPSA
TIETACSSSH VATHIACQSI QSGESDMAVV GGIGMLLVPE STMQLNNLGF LSAFGQSRAF
DASGAGYGRG EGCGIFILKR LDKAMEDGDT IRAIIRGSGV NSDGWTQGVT MPSGDAQASL
IEYVYKSNGL DYEGTQYVEA HGTGTKVGDP TEAEALHRTI GQPTPKRKKL WMGSVKTNIG
HLEAAAGAAS MVKGVLAMEH GFIPPTLHFK NPNPAIKFDE WQLGVPTKLM PWPACQTRRM
STSAFGMGGT NAHLVLERPN EPAIPILERG AIGVSRKNQK RLFVFSSHDQ AGFKRICDRL
VEHVDTLGPK SSNPDYLANL AHTLAVGRSG LTWKSSCFAE NIVELREHLT SSSLPEGAVR
AAGGQTRIGF VFTGQGAQWA RMGVELMDRK VFGKSVAKST ALLQEMGCEW DPVVELSKSQ
KESQLVKPEI SQPICTILQI ALIDELRSWG IRPAKVVGHS SGEIAAAYCM GALTHRDALA
AAYFRGKASA NVKRRGGMMA VGTTPEDAKK LITETKAQAT VACVNSPRSI TLSGDVDALE
ALRETFEKQG VFARRLKVDV AYHSSHMRSC SAEYQSSIMD LEPSELDGAN ESKEPILMVS
SVTGGLVDAE ALGPYYWIRN LISPVLFSDA LKELVCPADS GGSSDVDMLI EIGPHSALRA
PIEQILSHHD IKNVEYASML TRGESGSETI LGFAAELFRR GVPFDIAKAN DDAQCRLLTD
LPPYPFNHSQ QFRAESRLQR ETLTQQNPTK SLIGAERPSL DEHERVWRGF INLDDEPWLR
DHTVGSTVLF PGAAVITIVL EAAQQMAEAG KTIRSLTLRD ISFMAMMTLL EGTPTEVITH
VRPHLVATTG TTPATWWEFT VSSCTGVTSN VRNNCRGLFS INYEDSRSSH MEMELERFEG
DRVATYHQIK KECVEVISKQ AFYDTLARSA LAYGPHFQGV DNCRPGNGQT AFEVIVSDLG
ETFNKDKLTR PFLIHGGTLD SIFQAWVGST KDSNGPGSFG FEKPLLPKSI GELEISLDFP
GEVGYSLNGL STSKKHGFSE WSTDITMFDR NVSKLLLSVK DFHLAELEVE DADRPDRTEH
VDVDPAEISS EPKWNYALDF MSTQEIKQVV ETASSSDDKL MQFISLAIHQ RPNLEILELV
ESANQLRQTA VSKLPRGRLL PNQASCAILG GDYDNNNESA AAFGRIFGLD SSEAVPSDVA
PADLVIANFN ISNLEDIAER LVVLAKPEAR ILLIADKKVD SSVTSLADKG FDLVFSTEAD
SESLSLYCFG KKEEPQPERL TNGSTGQEVV ILEPSSLSAE SDRFSKDLQH ALDNIGYNVS
TVTDIHGAHA AKARIYVSLL EIEQPVLENL SQSEFEGLRD LLLNCDRLLW ITRGDGPSLQ
LVDGFSRTIR SEFAGVEFQV LHLSGKNSRQ GPSLAAQIVF KQSTESEFRE DDGHLQISRW
YRSVEEDDHI RNHLLDSIRT VSLPVGGNIE DNSSYRLAVG KPGLLNTLHF VSDDNTEAPL
ADNEVEMQVK ASGINFRDIM GSMGLLPVSG IGQEASGIVV RVGKLGASSL KPGDRISTLT
VGGTHATRIR CDYRVAKKIP EGMSFEEAAG IPVVHCTAYY ALVKLAKLRP GQSVLIHAAA
GGTGQAALQL AKHLGLTIFA TVGTDTKRAL IREKYGVPDE NIFHSRDGSF VKGIERATNG
RGVDCVLNSL SGELLRLSWG CLATFGTFVE IGLRDITDNM RLDMRPFAKS TTFSFINMVT
LLQENPDAMG EILESVFEMI HQNVLQPVFP VTVYPVGKVE EAFRLMQQGK HVGKMILSFA
AGDARAPVLC RAKDSFKLDP NATYLFIGGL GGLGRSMAVG FVACGARNIA FLSRSGDSKP
EAKAVVDELR ELGTRVQVYL GDVSDEASFR GAMEQCSREL PPVKGVIQMA MVLRDVVFEK
MKYDDWTTGL RPKVQGTWNL HTFFDKDRPL DFMIFFSSIA GVFGNPSQAQ YAAGNTYQDS
LAKYRRDRGL KAVSVNLGIM RDVGVIAEGD SHFMQQWEEV LGIREPAFHA LIKSIINGQL
ETSNIREAAK CPVQVTVGLG TGDILARNKI REPDYFRDPR FGALAVCSST STAAASSGEN
GVSIASQLAG LSNEADPEEA AGPIITKALV SKLAKILQVP PSEIDSSRPM YRYGVDSLVA
IEVRNWITKE MSANMSLMDI LGAMPMEQFA VQIAKKSKLV GGS
