RADS1_FLOCH
ID RADS1_FLOCH Reviewed; 2431 AA.
AC C5H885;
DT 31-JAN-2018, integrated into UniProtKB/Swiss-Prot.
DT 28-JUL-2009, sequence version 1.
DT 03-AUG-2022, entry version 67.
DE RecName: Full=Reducing polyketide synthase rads1 {ECO:0000303|PubMed:19101477};
DE Short=R-PKS rads1 {ECO:0000303|PubMed:19101477};
DE EC=2.3.1.- {ECO:0000305|PubMed:19101477};
DE AltName: Full=Radicicol biosynthesis cluster protein s1 {ECO:0000303|PubMed:19101477};
GN Name=rads1 {ECO:0000303|PubMed:19101477};
OS Floropilus chiversii (Chaetomium chiversii).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Sordariomycetidae; Sordariales; Chaetomiaceae; Floropilus.
OX NCBI_TaxID=2587399;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DISRUPTION PHENOTYPE, AND
RP DOMAIN.
RC STRAIN=CS-36-62;
RX PubMed=19101477; DOI=10.1016/j.chembiol.2008.10.006;
RA Wang S., Xu Y., Maine E.A., Wijeratne E.M., Espinosa-Artiles P.,
RA Gunatilaka A.A., Molnar I.;
RT "Functional characterization of the biosynthesis of radicicol, an Hsp90
RT inhibitor resorcylic acid lactone from Chaetomium chiversii.";
RL Chem. Biol. 15:1328-1338(2008).
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:19101477). The cluster encodes
CC only two apparent post-PKS enzymes, a cytochrome P450 monooxygenase
CC (radP) and a non-heme halogenase (radH) that introduce the epoxide and
CC the chlorine, respectively (PubMed:19101477). If this cluster includes
CC all the genes required for radicicol biosynthesis, the remaining
CC structural features of radicicol are presumably generated by the PKSs
CC rads1 and rads2 (PubMed:19101477). The C-2' ketone could arise if the
CC R-PKS rads1 and NR-PKS rads2 each carry out four iterations, in
CC contrast to the five iteration-three iteration split for the
CC hypothemycin PKSs (By similarity). The origin of the cis 5',6' double
CC bond is not known (By similarity). The radicicol R-PKS radS1 ER domain
CC may catalyze either double bond isomerization or reduction in the third
CC iteration (By similarity). {ECO:0000250|UniProtKB:B3FWU0,
CC ECO:0000269|PubMed:19101477}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:19101477}.
CC -!- DISRUPTION PHENOTYPE: Completely abolishes the production of radicicol
CC (PubMed:19101477). {ECO:0000269|PubMed:19101477}.
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:19101477). {ECO:0000305|PubMed:19101477}.
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DR EMBL; EU980390; ACM42406.1; -; Genomic_DNA.
DR AlphaFoldDB; C5H885; -.
DR SMR; C5H885; -.
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 3: Inferred from homology;
KW Acyltransferase; Multifunctional enzyme; NADP; Oxidoreductase;
KW Phosphopantetheine; Phosphoprotein; Transferase.
FT CHAIN 1..2431
FT /note="Reducing polyketide synthase rads1"
FT /id="PRO_0000443054"
FT DOMAIN 2346..2423
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:19101477"
FT REGION 13..443
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:19101477"
FT REGION 558..895
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:19101477"
FT REGION 946..1264
FT /note="Dehydrogenase (DH) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:19101477"
FT REGION 1705..2023
FT /note="Enoyl reductase (ER) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:19101477"
FT REGION 2048..2228
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:19101477"
FT ACT_SITE 1822
FT /note="Phosphocysteine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00590"
FT MOD_RES 2383
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2431 AA; 263595 MW; A2F64A0B31192BAE CRC64;
MPSATGNGAR APIAIIGLAC RFPGDASNPS KFWDLLKEGR EAYSERTNRY NEDAFHYPGG
DNRRQNVLPV KGGYMLKQDP YAWDAAFFNI TAAEAIAFDP KQRIAMEVAY EAFENAGMTL
QKVAGTQTAC YIGTSMSDYR DSIVRDFGNY PKYHLLGTSD EMISNRISHF FDIHGPSATI
ETACSSSHVA THIACQSLQS GESEMALAGG VGMLLVPEST MQLNNLGFLS PFGQSRAFDE
TAGGYGRGEG CGMYVLKRLD KAIQDGDTIR AIIRGSGVNQ DGWTQGVTMP SGDAQASLIK
YVYESNGLDY GATQYVEAHG TGTQAGDPTE AAAIYRTIGQ GGQKTNPWRK KLWIGSVKTN
IGHLEAAAGA ASVIKGVLAM EHGFIPPTIH FKKPNPAVKL EEWNLAVPTK LMPWPACQTR
RMSTSAFGMG GTNAHIVLER PNDQALREMS NRSRPLVNGM GEGNNTKKRL FVFSSHDQAG
FKRLADAFVE HLDRLGPAAA SPEYLANLAY TIATARSGLS WRASCSAESA AELREQLLTT
LGENATRASS GQQPRIGFVF TGQGAQWARM GIEMLERRVF GDSVARSAAL LREMGCDWDP
VTELARAQKE FRLGVPEISQ PICTVLQIAL VDELRSWGIT PSKVVGHSSG EIAAAYCIGA
LSHSDALAAA YYRGKASAGI KQRQGGMMAV GCSPEAAKKL MTETSLRATV ACVNSPSSVT
LSGDVGTLEA LRAVLEERGV FARRLKVEVA YHSPHMHSCS TEYTAAIQHL EARAAAAHDE
EDDRQQRQSP IVMVSSVTGS EVDPEMLGPY YWVRNLISPV LFADAVKELV SPVGEEGNAV
DMLVEIGPHS ALQGPTEQTL SHHGIKNVRY LSMLTRGENA LTTSLNLAAE LFRRGVVVDV
AKANDDTHCR LLTDLPPYPW NHSQTFRADS RIQRELVAQK FPTKSILGAE LPSMDETERV
WRGFIRLEEE PWLRDHTVGT TVLFPGAGVI SMVLEAAQQM VEPGKTARAF TLRDISFMAL
MALTDGVATE VITHMRPHLM ATTGSTPAAW WEFTVSSCTG VTGPLRNNCR GLISIAYEDT
RSPHMIREDA GIEAARIADY HRILRECPET CSKERFYDRL AQSALRYGEI FRGVENCHPG
NGKTAFEVKL TDIGETFTRG KLARPFLIHA AALDAVLQAW VGTTSNSNGP GSFGFDAPML
PKSISEMEIS ARIPAEVGYV MPGFSRSKRH GFNEWSADIT MLDTGLSRVF LSIADFRLAE
LEVDDAAKPD RDTVDVDPAE IASEVHWNFA LELLKPAEIS RVVSSVGAET AHERLVELVR
MAIHQRPAVD VIELVASAEE LPDAVMSKLP QGIILPTQVR YGVVKGSADS THAANIKEDI
LGRPFALGAP LAADTAPADL FVIPHRVSKN PKDLDTVWES LACLTKSDAT ILMVAAAAAT
TTDNGPISST APELVAAKGF ELISCTPTST DSLALYHYAT KKNTQPERLT NGSVGERVVI
LEPYKSSTAI RTFSNELREL LEDQGYVVST RTDIVGARAD AGVGASLSAK TCVSLLELEQ
PVLDNLSEAD FQSIRALILN CERLLWVTRG DSPSMRLVDG FARCIRNEIA GIKFQLLHLS
SGEGPQHGPG LAARILLAPT ADNEFREHDG LLQVSRIYRS LAENDQIRNH LHDSVRVASL
PSGNFQDGKS MAGAPPLRLS IGRPGLLNTL HFVPEEESTA LAPLADNEVE LEVRASGINF
RDIMGSMGLL AVTGIGQEAS GVVVRTGRLG AEAASLKPGD RVSTLTAGGT HATRIRCDYR
VAQRVPEAMS FEEAAGVPVT HCTAYYALVR LANLRRGQSV LVHAAAGGTG QAAVQLAKHM
GLVVYATVGT DKKRRLMMEE YGIPEEHIFS SRDGSFVKGI KRITGGRGVD CVLNSLSGEL
LRLSFSCLAT FGTFVEIGLR DITDNMRLDM RPFAKSTTFS FINMVTLLQQ DPDTLGEILG
EVFKLLREGI LRPAQPVTVY PVGQVEEAFR TMQQGKHLGK MILSFTADHG RAPILYRAKD
SLKLDPNATY LIVGGLGGLG RSLAMEFAAS GARYIAFLSR SGDAKPEARA VIDQLAARGV
QARVYRADVA DEASFLQAME DCTQQLPPIK GVVQMAMVLR DVVFEKMKYE EWATGLRPKV
QGTWNLHQYF DHERPLDFMI FCSSIAGVFG NPSQAQYAAG NTYQDALASY HRARGLKAVS
VNLGIMRDVG VIAEGDSHFM QTWEPVLGIR EPAFRALMKS LINGQVQHEH HDGRWPCPPQ
VCVGLGTGDI LATHNLARPA YFEDPRFGPL AVTSVTAAGS SSSGDGATVS LASRLSEVST
NKDPAVAAAI ITEALVKTMA DILRIPPSEV DPSRPMYRYG VDSLVALEVR NWITKEMKAN
MTLMEILAAV PMETFAVQIA KKSKLLVGLA A
