FUMOS_CORFA
ID FUMOS_CORFA Reviewed; 4138 AA.
AC A0A167LUQ4; A0A0E3Y5V5;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 06-JUL-2016, sequence version 1.
DT 03-AUG-2022, entry version 37.
DE RecName: Full=Fumosorinone synthetase {ECO:0000303|PubMed:25857260};
DE EC=2.3.1.- {ECO:0000305|PubMed:25857260};
DE EC=6.3.2.- {ECO:0000305|PubMed:25857260};
DE AltName: Full=Fumosorinone biosynthesis cluster protein B {ECO:0000303|PubMed:25857260};
DE AltName: Full=Hybrid PKS-NRPS synthetase fumoS {ECO:0000303|PubMed:25857260};
GN Name=fumoS {ECO:0000303|PubMed:25857260}; ORFNames=ISF_08690;
OS Cordyceps fumosorosea (strain ARSEF 2679) (Isaria fumosorosea).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Cordycipitaceae; Cordyceps.
OX NCBI_TaxID=1081104;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DISRUPTION PHENOTYPE, DOMAIN,
RP AND PATHWAY.
RC STRAIN=ARSEF 2679;
RX PubMed=25857260; DOI=10.1016/j.fgb.2015.03.009;
RA Liu L., Zhang J., Chen C., Teng J., Wang C., Luo D.;
RT "Structure and biosynthesis of fumosorinone, a new protein tyrosine
RT phosphatase 1B inhibitor firstly isolated from the entomogenous fungus
RT Isaria fumosorosea.";
RL Fungal Genet. Biol. 81:191-200(2015).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ARSEF 2679;
RX PubMed=27071652; DOI=10.1093/gbe/evw082;
RA Shang Y., Xiao G., Zheng P., Cen K., Zhan S., Wang C.;
RT "Divergent and convergent evolution of fungal pathogenicity.";
RL Genome Biol. Evol. 8:1374-1387(2016).
CC -!- FUNCTION: Hybrid PKS-NRPS synthetase; part of the gene cluster that
CC mediates the biosynthesis of fumosorinone, a 2-pyridone alkaloid that
CC acts as an inhibitor of protein tyrosine phosphatase 1B which is
CC implicated asa negative regulator of insulin receptor signaling and a
CC potential drug target for the treatment of type II diabetes and other
CC associated metabolic syndromes (PubMed:25857260). The polyketide-amino
CC acid backbone of fumosorinone is first assembled by the PKS-NRPS hybrid
CC fumoS (PubMed:25857260). The PKS modules condense one acetyl-CoA
CC starter unit with 7 malonyl-CoA units, programmed C-methylations
CC occurring after the first 3 and the sixth extensions, and cycles of
CC full reduction occurring after the first 2 extensions (Probable).
CC Because fumoS lacks a designated enoyl reductase (ER) domain, the
CC required activity is provided the enoyl reductase fumoC (Probable).
CC Upon formation of the polyketide backbone on the thiotemplate, the
CC polyketide is transferred to the NRPS module and linked to tyrosine to
CC produce the acyltetramic acid intermediate called prefumosorinone A
CC (Probable). The cytochrome P450 monooxygenase fumoA then probably
CC catalyzes an unprecedented oxidative ring expansion of prefumosorinone
CC A to form prefumosorinone B which contains the 2-pyridone core of
CC fumosorinone (Probable). The cytochrome P450 monooxygenase fumoB might
CC hydroxylate the nitrogen of prefumosorinone B, but not the acyltetramic
CC acid prefumosorinone A, to form fumosorinone (Probable).
CC {ECO:0000269|PubMed:25857260, ECO:0000305,
CC ECO:0000305|PubMed:25857260}.
CC -!- DOMAIN: FumoS has the following domain architecture: KS-MAT-DH-MT-KR-
CC ACP-C-A-T-R. The PKS module (domains KS to ACP) is responsible for the
CC biosynthesis of the polyketide chain and catalyzes three Claisen
CC condensations, as well as beta-keto processing and methylation. The
CC downstream NRPS module contains the condensation (C), adenylation (A),
CC and thiolation (T) domains and catalyzes the formation of the L-
CC tyrosinyl-thioester and the amide linkage between L-tyrosinyl-thioester
CC and the polyketide. The bimodular assembly line is terminated with a
CC putative reductase (RED) domain that facilitates formation and release
CC of the tetramic acid product. {ECO:0000305|PubMed:25857260}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of fumosorinone
CC (PubMed:25857260). Leads to more developed aerial mycelia but does not
CC affect insect pathogenesis (PubMed:25857260).
CC {ECO:0000269|PubMed:25857260}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the NRP synthetase
CC family. {ECO:0000305}.
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DR EMBL; KP737857; AKC54422.1; -; Genomic_DNA.
DR EMBL; AZHB01000034; OAA53529.1; -; Genomic_DNA.
DR RefSeq; XP_018700480.1; XM_018852293.1.
DR SMR; A0A167LUQ4; -.
DR EnsemblFungi; OAA53529; OAA53529; ISF_08690.
DR GeneID; 30024982; -.
DR OrthoDB; 19161at2759; -.
DR Proteomes; UP000076744; Unassembled WGS sequence.
DR GO; GO:0016746; F:acyltransferase activity; IEA:InterPro.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
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:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.1200.10; -; 2.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.30.559.10; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR010071; AA_adenyl_domain.
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; IPR045851; AMP-bd_C_sf.
DR InterPro; IPR020845; AMP-binding_CS.
DR InterPro; IPR000873; AMP-dep_Synth/Lig.
DR InterPro; IPR042099; ANL_N_sf.
DR InterPro; IPR023213; CAT-like_dom_sf.
DR InterPro; IPR001242; Condensatn.
DR InterPro; IPR013120; Far_NAD-bd.
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; IPR013968; PKS_KR.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF00668; Condensation; 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; PF07993; NAD_binding_4; 1.
DR Pfam; PF00550; PP-binding; 2.
DR Pfam; PF14765; PS-DH; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 2.
DR SUPFAM; SSF47336; SSF47336; 2.
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 TIGRFAMs; TIGR01733; AA-adenyl-dom; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS50075; CARRIER; 2.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 3: Inferred from homology;
KW Ligase; Methyltransferase; Multifunctional enzyme; Oxidoreductase;
KW Phosphopantetheine; Phosphoprotein; Reference proteome; Repeat;
KW Transferase.
FT CHAIN 1..4138
FT /note="Fumosorinone synthetase"
FT /id="PRO_0000451336"
FT DOMAIN 2507..2587
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:25857260"
FT DOMAIN 3680..3759
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:25857260"
FT REGION 18..458
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25857260"
FT REGION 590..921
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25857260"
FT REGION 990..1306
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25857260"
FT REGION 1456..1650
FT /note="Methyltransferase (MT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25857260"
FT REGION 2205..2379
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25857260"
FT REGION 2587..2683
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2701..3128
FT /note="Condensation (C) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25857260"
FT REGION 3162..3564
FT /note="Adenylation (A) (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25857260"
FT REGION 3813..4045
FT /note="Reductase (RED) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25857260"
FT COMPBIAS 2621..2673
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 2547
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3719
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 4138 AA; 445360 MW; 1CDDC5C1986B8295 CRC64;
MSPTTQHEPG SPRVPEPIAI VGSACRFPGG SSSPSKLWDL LREPRDVLRE LPPERLNLNR
YYHPDGERHG STNVANRAYV LDEDVARFDA GFFGISPLEA AGMDPQQRLL LEVVHEATEA
AGIPLAQLRG SPTSVHVGVM TNDWSHLQRR DPETMPRHTA TGAAASIIAN RVSYVFDLRG
ASETIDTACS SSLVALHSAA RALRAGDCTR AVVAGVNLIL DPDPFVFEAK LGMLSPGSRS
RMWDKEADGY ARGEGVAAVV LKTLRDALRD GDEVAGVVRA TGVNSDGTGG GGGLTMPSAE
AQTALIRRTY EEAGLDPVAD RPQFFECHGT GTKAGDPVEA RAISEAFVKG HRGEEGVPTV
KQPLYVGSIK TVVGHLEGCA GLAGVIKVLL SLKHGVIPPN LLFNELNPDI AQYYGPLNIP
TKAKPWPKLA PGVPLRASVN SFGFGGTNAH AIIERYDATQ SYVVALKAGI PHLSRPITHR
DSSDVSIPAP ILLSARTGGA LWRTVDAYAR HLRQHPELSL ADLSRFLHER RSTHRVRAHF
SGASREALLD SMDAFVRTHA ADAKSAATQG RIGHAPLLID PKETPGVLGV FTGQGAQWPA
MGRDMMRASP LFRRTIAECE GVLRALPGDD APEWSLAEEL TKEAPASRLA EAAIAQPLCT
AVQLALVGAL RAAGLRFDAV VGHSSGEIAA TYAAGIITLQ GAMQIAYYRG FHAKLARGPA
GEAGGMLAVG LSPAEARELC ARPEFTGRLQ VAACNAPKSV TLSGDKEVVA AAREMLVAQG
AFARELRVDT AYHSHHMLPC AAPYLESIRK CDVQVSRPTP GTCQWSSSVR GDAELLRADR
SLEDLKGPYW VANMVQTVQF SRALEASIWH GGPFDLAVEV GPHPALKGPT EQTLKGVYGS
VPFYTGVLKR DAPDAVSFST AIGSVWAHLG PDFVDVPGYC RSVFSETGHD QEGPVTFVPD
LPAYAWDHEE THWRESRISK RYRTGRDGYH ELLGRRAVDD NEREVRWRNL LAVRDLPWTR
GHTILGEVLL PGAAYVSMAL EAGRRLAEDR GREARLLEVS EVDILRPVVV ADGKDATETL
FTVRILKEDL STDYKSGGGL IKASFSFCVY SSASSTAIAH TCEGLIDVHL GPRLGSESED
EGSVPQLPQR QAPAPNLQEI DCEKLYAQFG TIGLEYSGIF RRMTSSRRHL GHATASASWA
AADLGDAYMV HPAVLDVAFQ TIFVAHAHPD SGQVNAALLP SRIERVRVAP SPAMQRIDGI
LSAEVDSWIL HQTATSVTGN LDVHDADTGA PLLQVEGFEV RSVGERDAAA DRLIFAETAW
GPDVSVAGGL SDPIRDEAAD ATVKGLAEAS ERVSLFYARR LMAELSAEDR ARASWYHERL
LQALDHHLER LKGGVHPHLR AEWLADDDEV VRAIDAAFPK TVELQMLHAV GRNMASVVRG
EKHMLEVMRV DNMLDRFYAE DKGMQQVNIF LANAVKEISF KFPRCKILEI GAGTGATTSA
VLHALDDAFD TYTYTDLSVG FFETAMERFA DSRHKMVFAA LDVEKDLASQ PGFAPHSYDL
IIAANVLHAT RDMAVTLRNV RALLRPGGYL VLNEHTGAGS LCATFNFGGL EGWWLAEEED
RRRSPLLSTA RWDAQLRRAG FSGADHVAHD IPEGGEGGRQ ISLIVSQAVD ERFWARVSPL
SEMAELQEQE EEEMPLLLIG GKMTATARIF KEVRKLLPRR WRERVRLVDC VDSLDVEALP
ARCDVICLQE LDAALFATPM TPRRLQILQT LLMNTANLLW VTHAQTSGSA TPRAAMFRGI
TRVMAGEIPQ INTQVIGVEP ATVPSSTARH LLEAFLRLQS EHTRIATNSD GDDAQQSALW
SHEPEIDILP DGTVMIPRVR LNRSLNETYN ASSRTVAKTV DASCVPVQAV AGPTKMQLQP
ADEQTSLANG TDSTVRVKVE FTLHVPQAPD GTNLYLVCGW TLPTEAPDGT PNAVLAVSTV
NASIIEVPSA SAAVVADDDM QPDLLLRIFD HLAAQAVQVQ LNPTGEHKAR ALIYGADERL
AQLISTQSTF RDNKVYFASS QRWVPDDWIK VHPLSSKFAL SQALPYGVQV FIDCLGTGES
VDGRKMIVSC LPAARRVRRL DASLLLELPQ FSAALASAYS HAKSVTCPDA GEPSRVDRFH
ATELAGRPSN SFASSVYITS WQDLGAVQVA TPPLETQGMF RSDRTYLMVG AAGGVGTSIC
RWMVRNGARH VVVTSRTPTA DPVMLAEAAH HGADVRVLPM DVCDRLAVHA LVDTIRATMP
PIAGVCNAAM VLRDKLFLDM DVDILNDTLG PKVDGTETLD ALFSDDAALD FFVLLGSAAT
VASNAGQANY HCANLYMDAL VRRRRARGLA ASIIHVGFVC ETGYVARLVD EARALTQRDA
MRVTTLSETD VHHAFAQAVR GGRPGRSGGS HSIVMGIEPP SKALEAGRSL EAVRRKALWL
SDPRFGHMVP YSTAASQTAV EQSAAADASA GGGSVGQQVA EASTEEEAAA AVRRAFSAKL
EGILLLPPSS IGEDGAGRPV TDLGIDSLVA VEIRTWFLKQ LRVDVPVMKI LGGSTIGQLS
TLAAKLARQQ SPRKEGQMAG KEQGLPSPET QDKLVDDKEQ KVQVTSSLAK ADSLTQEMQA
SAHSHSDSAT NPTPSSTASE ADDSNSQSTR STSTEPKTED KVSAHVQLEP ATADHHPKIL
REAPMSAAQA RIWFLAEHMA EPDAYNMVFH YRVRGPLHLA RLRRALHAVA AHHECLRMSF
RADPHTGQPM QGLLACSAFQ MTIRDEGDVE EELRRLRTRA WRLELGETLE IVALPGGELL
FGYHHIVMDG IGWAVVLADL DRAYRMLPLD KAAAGSHVEF SEAQRQQERE GALDEPLAFW
QAEFETIPEP LPQLSVSSPQ RSVAAAGTHR VLRELPPARG AAIRAAGRQL RVSPFHLHLA
VLQVVLARLA GIEDVCVGIV DANRGDARAA RMVGCFVNML PVRNQVRPGA SLAEVARGAA
SKALAAFANG AAPLDRILDR VQAPRPVGGT PLFQAALNYR PASALMHEAP LGAECRMELV
PGDIKDADNP FEVSVLLSEL PGGGLGVEMF CQKAVYNIDG SEALLDAYVN VLGDFMTDAS
QRVRECAVYR QADVDEALTL GKGPEIKFGW PATLSERVMN ICQKNSARTA IKDGSMTLSY
ASLASKVNDV ASAIVSAGSG VGSRIAVLCE PSVDAIVAML AILHIGAVYV PLDISLPEAR
HVALVSNCTP SLIVCHKATL ERTHRLSTPG YESAQELVID DLPPSSKQID SAPLRAQPDA
PAILLYTSGT TGTPKGVLLT QANFANHIAL KSAHLGLDRD EVILQQSSLG FDMSLVQIFC
ALGNGGCLVI VPPDARRDPV ELTSIVQQHE VSLTIATPSE YLAWLQYGSG CLAQATAWRH
LCMGGEPISQ LLKDELRRLG RKNLKVTNCY GPTETTAAVS FQLIDLESDS CSSQLGSEVS
RYAVGKPLAN YSIRIMDPVG AWLPVNHTGE IVTGGAGVAL GYLGLSEETR AKFVQVDGEP
GRFYRTGDTG RLLPDGTLLC FGRIEGDSQV KLRGLRIELQ EVEAAILQAS EGLLQAAGVS
CRGDMLVAHC TLSPGKESTE TDKTALLRRL SEVLPQFAVP AAIHIVPSLP NNSNGKLDRK
AIAALPLPTS DCAAHASSSE KMTIQEGELR LLWERVLPRD AAGSRITPAS DFFLRGGNSL
LLMKLQAAIR DAMDVRVPTR ALYQASTLSG MTRCVLAQRE RQRRDEPPAE DIDWAAEVAV
PPELLARADE LNSSAAAASL RPRKTTGGLE ILLTGATGFL GGQLLRHLLR SPAVSRIHCV
AVPADEREHL EAGSEANGSS GKVACHTGNL AAADLGLAAA QRARLAQSVD VIVHAGAAGH
CLNTYATLSA PNLSSTKSLA ALALARSPPI PLFFASSNRV VLLTGETAPA SPSSVASSLP
PADGAQGYTA SKWASEVFLE SLTNAVTSPW RVSIHRPCAL VGDGVPNTDA LNVILRYAVE
MRCVPSLPRE RARGYLDFGT VDAVVAEMAA DVLALADEEE GGAGVRYRHH SGGVKVPIHE
FRAHMDKKYG ERFESVDLAA WIPRAVEAGM DPLISAYLET FLETDEPLIF PYMGGKSD
