G433_FUSSX
ID G433_FUSSX Reviewed; 2510 AA.
AC A0A6S5ZY48;
DT 23-FEB-2022, integrated into UniProtKB/Swiss-Prot.
DT 02-DEC-2020, sequence version 1.
DT 03-AUG-2022, entry version 7.
DE RecName: Full=Highly reducing polyketide synthase g433 {ECO:0000303|PubMed:32139880};
DE Short=HR-PKS g433 {ECO:0000303|PubMed:32139880};
DE EC=2.3.1.- {ECO:0000305|PubMed:32139880};
DE AltName: Full=1233A biosynthesis cluster protein g433 {ECO:0000303|PubMed:32139880};
GN Name=g433 {ECO:0000303|PubMed:32139880};
OS Fusarium sp.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Nectriaceae; Fusarium.
OX NCBI_TaxID=29916;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, INDUCTION, DISRUPTION
RP PHENOTYPE, DOMAIN, AND PATHWAY.
RC STRAIN=RK97-94;
RX PubMed=32139880; DOI=10.1038/s41429-020-0295-4;
RA Kato S., Motoyama T., Uramoto M., Nogawa T., Kamakura T., Osada H.;
RT "Induction of secondary metabolite production by hygromycin B and
RT identification of the 1233A biosynthetic gene cluster with a self-
RT resistance gene.";
RL J. Antibiot. 73:475-479(2020).
CC -!- FUNCTION: Highly reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of 1233A, a natural compound known as an
CC inhibitor of HMG-CoA synthase in the mevalonate pathway and with
CC antibacterial and antifungal activities (PubMed:32139880). The highly
CC reducing polyketide synthase g433 gene is responsible for the 1233A
CC backbone biosynthesis and the cytochrome P450 monoxygenase g430
CC catalyzes oxidation of the backbone (Probable).
CC {ECO:0000269|PubMed:32139880, ECO:0000305|PubMed:32139880}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:32139880}.
CC -!- INDUCTION: Expression is increased upon exposure to hygromycin B.
CC {ECO:0000269|PubMed:32139880}.
CC -!- DOMAIN: Multidomain protein; including a ketosynthase (KS) that
CC catalyzes repeated decarboxylative condensation to elongate the
CC polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects
CC and transfers the extender unit malonyl-CoA; a dehydratase (DH) domain
CC that reduces hydroxyl groups to enoyl groups; a methyltransferase
CC (CMeT) domain responsible for the incorporation of methyl groups; an
CC enoylreductase (ER) domain that reduces enoyl groups to alkyl group; a
CC ketoreductase (KR) domain that catalyzes beta-ketoreduction steps; and
CC an acyl-carrier protein (ACP) that serves as the tether of the growing
CC and completed polyketide via its phosphopantetheinyl arm.
CC {ECO:0000305|PubMed:32139880}.
CC -!- DISRUPTION PHENOTYPE: Impairs the ability to produce 1233A and its
CC hydrolysis product 1233B. {ECO:0000269|PubMed:32139880}.
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DR EMBL; LC516401; BBU37368.1; -; Genomic_DNA.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0008168; F:methyltransferase 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:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite 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 Gene3D; 3.40.50.150; -; 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; 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; IPR013217; Methyltransf_12.
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; IPR029063; SAM-dependent_MTases_sf.
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; PF08242; Methyltransf_12; 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; SSF53335; SSF53335; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 2: Evidence at transcript level;
KW Acyltransferase; Methyltransferase; Multifunctional enzyme; NADP;
KW Oxidoreductase; Phosphopantetheine; Phosphoprotein; Transferase.
FT CHAIN 1..2510
FT /note="Highly reducing polyketide synthase g433"
FT /id="PRO_0000454632"
FT DOMAIN 2419..2496
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 1..54
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 61..480
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000250|UniProtKB:S3D9F1, ECO:0000255"
FT REGION 574..880
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000250|UniProtKB:S3D9F1, ECO:0000255"
FT REGION 942..1226
FT /note="Dehydrogenase (DH) domain"
FT /evidence="ECO:0000250|UniProtKB:S3D9F1, ECO:0000255"
FT REGION 1395..1574
FT /note="Methyltransferase (CMet) domain"
FT /evidence="ECO:0000250|UniProtKB:S3D9F1, ECO:0000255"
FT REGION 1787..2097
FT /note="Enoyl reductase (ER) (ER) domain"
FT /evidence="ECO:0000250|UniProtKB:S3D9F1, ECO:0000255"
FT REGION 2122..2296
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000250|UniProtKB:S3D9F1, ECO:0000255"
FT COMPBIAS 12..54
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 229
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2456
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2510 AA; 274475 MW; 8F2739450F49405A CRC64;
MAPGRTDVTV AENGNGLHTA HNGVSNGTSN GTNGTSHTSN GTNSSAKTTS NGVHSHEDIP
IAIVGMGLRL PGGIGTEEDL WDTLINKKDQ RQRVPADRWN VDAFYSKTNK RGTVKTEHGY
FLADEDLQQF DTSFFSITRN ELEKLDPQHR LLLEVTRECL ENAGELDWRG KDIGCYVGVF
GEDWLDLHAK DSQDFGIYRI TGAGDFVLAN RISYEYDLKG PSITVKTACS SALICLHMAC
DAIRSGEISS AIVGGANLLM SPTMTIAMSE QGVLSGDGSC KTFDAAADGY ARAEAVNALY
VKRLDHAIRD GNPIRGIVRG TGSNCDGKTA GLSHPSPESH EALIRRTYQQ AGIDDFCQTA
FVECHGTGTA TGDPLETSAI GNVFGEKGVY ITSVKPNVGH SEGASGITSC IKAILAMEKK
TIPPNIKFNN PNPQIPFKKA KLQVPVEPTP WPQDRQERVS INAFGIGGAN AHAVIDSAES
YGVNSMRATR SSTEPLRQSL VVFSSNHMNS ARNGTANLQK YLTKHPGSVK DLAYTTGVRR
ERLPYRSFAV SDGSAPLEFT APSRTPATTP GVTFVFTGQG AQWATMGVNL LEEFPSAEED
FKNLDKALSQ LPYPPSWSIA DELLRSKEES RLDQAEFSQP LCTAVQVVIV NLLRAWNISP
SRVIGHSSGE LAAAYASGAI TAAEAIIGAY YRGLVTKQQA RPGAMAAVGF GREDVASYLT
EGVTIACENS PESTTLSGDA DKIDAVIAKI KESHPDVLAR RLRVEMAYHS YHMADVGTRY
QELLEPHVSS TRPDVPFYST VLEKVITEKS AMNASYWRRN MESPVLFNTT MAKLLTDECA
NNLFLEIGPH SALAGPLRQI FKKHQPDALY VPTLVRGQND TTSLLSTAGN LFVKGLAVDI
GAVNDGGSIL TDLPTYPWHH EDTFWDESRL TREWRKRKFP RHDLLGCQVF EGSSLEPTWR
NMLCLEDVPW IRDHVIGPDI VFPGAGYIAM AGEAIRQVAD AQDYTVRNLS VKSAMILHEP
VTTEILFSLR PHRLTTSLDS AWYEFTVSSH NGTGWTKHCT GQVKAGRADS GSVSEPPQAT
TLPRKVSSTR WYQTMSKVGI NYGPTFQGLE DVSAHPVNNF AVAKVTNTVD PNESTYQLHP
TTTDYAIQLF SVAAWKGQAR DFVQMPLPAY FGEVYMKRPQ TNEQLQLSSN VTVTARGAVH
GDGFATVGGE VVLEFRNLRL APAADDTGGD DQDPHAGVRL QWKPDVAFLD SKDLIRTTKS
IRSCYPTVQR LLLLCSIECT ERLASLPPSG VEHLEKFKTW LAAHVEQAKA DGYEAVDDVN
SLFALSRDDR LSLIETTAQE VKASYAEAVG NAICRVFENV EGIFTSEADA LDLLMQDDIL
RKIYDLVIEF WDFKDFLGLV SHDKPNLKVL EIGAGTGATT ALILDGLVSE LGEQMFYSYT
YTDISAGFFV QAKERFKNVH SIEYAVLDIS QDPAEQGFEL GSYDLVIATN VLHATPSLQE
TLVNVRKLLQ PKGKLMLQEL CSSTKWFNFI VGVLPGWWLG EPDGRPEEPY VGPERWAREL
TQAGFDGAEA VIYDEEKPYH TNATIIAHPL VEPKVNKKIS ILTTDPNGAA ATLLAQSLTR
QNFMVDFCSF QDAPQSDHDI ISVLDLEGRP FLADISADKF HSLQTFITKL SSSGMLWLTK
SAQMNSSEPE YAQIVGLARS VRNELSIDLA TVEMDNTQDE TTFNRVINIL SKFQNRSKNL
DIDPEFEYAI SNGVINISRF HWISVSNELA AGTDSTAPKT LEIGKRGSLK TLRWVQRSEI
KLIGDEVAVE VRAAGMNFKD ILISMGIVDG NVDDGNGLGC ECAGVVTQVG PDAPFHVGDR
VAIIGGDSYS TVLKTTSTLC ARIPDNLSFE DAATMPCVYT TVIHSLLDLA KIEKDQTVLI
QSACGGIGIA AINICRMIFA TVGSQEKIDY LMSTFGIPRN HIFNSRNSSF LPDVMRETSG
VGVDVVLNSL SGDLLHASWK CVAEFGKMVE IGKRDFIGQG KLAMEAFEAN RTFYGVDFAP
IAEKRPYIIK RLLERTMEFF RLGAIQPIRP IKFFDATQIE DALRYMQKGQ HMGKLVIQFP
TDHSQLTSSR GNNRLVLRSD ASYLLVGGLG GLGRSISTWM VEHGARHFIY LSRSGGKGPD
DAAFVQEMNA AGCTVQITAG SVANLADVQR AINQAEYPVA GVLQMSMVLR DASFPNMTHD
EWQAANLPKI KGTWNLHEAF ASQPLDFFVL FSSFSGLLGH WGQANYAAAN TFLDAFAQYR
HGLGLPASVL DISIIEDVGW VSQEPGHLEQ LKATAAYCLK EQHLLDSLEL AITKSAPQTW
EPKSPMDGYM NASQIGLGMR MTMPIAADAN RCIWKRDIRM GLYRNLENSG VDDAGTGNEG
LREFLTGVTT NPESLKEPSS VSFLANEIGS TLFSFLMRPI EELDVKQPLS AVGLDSLVAI
ELRNWSRQRL GVELSVLEIL GAASIEKLGE AAAEGLLVKL GGATTNGDAQ
