ID SPKS1_STRTC Reviewed; 2824 AA.
AC A0A384XH94;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 05-DEC-2018, sequence version 1.
DT 27-NOV-2024, entry version 24.
DE RecName: Full=Highly reducing polyketide synthase stpks1 {ECO:0000303|PubMed:30258052};
DE EC=2.3.1.- {ECO:0000269|PubMed:30258052};
DE AltName: Full=Strobilurin A biosynthesis cluster protein pks1 {ECO:0000303|PubMed:30258052};
GN Name=stpks1 {ECO:0000303|PubMed:30258052};
OS Strobilurus tenacellus.
OC Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Agaricomycetes;
OC Agaricomycetidae; Agaricales; Marasmiineae; Physalacriaceae; Strobilurus.
OX NCBI_TaxID=41251;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], INDUCTION, FUNCTION, CATALYTIC ACTIVITY,
RP PATHWAY, AND BIOTECHNOLOGY.
RC STRAIN=CBS 621.79;
RX PubMed=30258052; DOI=10.1038/s41467-018-06202-4;
RA Nofiani R., de Mattos-Shipley K., Lebe K.E., Han L.C., Iqbal Z.,
RA Bailey A.M., Willis C.L., Simpson T.J., Cox R.J.;
RT "Strobilurin biosynthesis in Basidiomycete fungi.";
RL Nat. Commun. 9:3940-3940(2018).
RN [2]
RP BIOTECHNOLOGY.
RX PubMed=563391; DOI=10.7164/antibiotics.30.806;
RA Anke T., Oberwinkler F., Steglich W., Schramm G.;
RT "The strobilurins--new antifungal antibiotics from the basidiomycete
RT Strobilurus tenacellus.";
RL J. Antibiot. 30:806-810(1977).
RN [3]
RP BIOTECHNOLOGY.
RX PubMed=6271595; DOI=10.1016/0014-5793(81)81190-8;
RA Becker W.F., von Jagow G., Anke T., Steglich W.;
RT "Oudemansin, strobilurin A, strobilurin B and myxothiazol: new inhibitors
RT of the bc1 segment of the respiratory chain with an E-beta-methoxyacrylate
RT system as common structural element.";
RL FEBS Lett. 132:329-333(1981).
RN [4]
RP REVIEW ON BIOTECHNOLOGY.
RX PubMed=29711574;
RX DOI=10.1002/(sici)1521-3773(19990517)38:10<1328::aid-anie1328>3.0.co;2-1;
RA Sauter H., Steglich W., Anke T.;
RT "Strobilurins: evolution of a new class of active substances.";
RL Angew. Chem. Int. Ed. 38:1328-1349(1999).
RN [5]
RP REVIEW ON BIOTECHNOLOGY.
RX PubMed=12146165; DOI=10.1002/ps.520;
RA Bartlett D.W., Clough J.M., Godwin J.R., Hall A.A., Hamer M.,
RA Parr-Dobrzanski B.;
RT "The strobilurin fungicides.";
RL Pest Manag. Sci. 58:649-662(2002).
CC -!- FUNCTION: Highly reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of strobilurin A, an antifungal
CC polyketide that contains a key beta-methoxyacrylate toxophore that
CC targets the complex III of the mitochondrial electron transport chain
CC (PubMed:30258052). Strobilurin biosynthesis begins with construction of
CC benzoyl CoA by step-wise elimination of ammonia from phenylalanine by
CC the phenylalanine ammonia-lyase str11, oxygenation by str8 and retro-
CC Claisen reaction to form benzoic acid, which is activated to its CoA
CC thiolester benzoyl CoA by the dedicated CoA ligase str10
CC (PubMed:30258052). Benzoyl CoA forms the starter unit for the highly
CC reducing polyketide synthase stpks1 that produces the polyketide
CC prestrobilutin A (PubMed:30258052). The FAD-dependent oxygenase str9
CC then catalyzes the key oxidative rearrangement responsible for the
CC creation of the beta-methoxyacrylate toxophore (PubMed:30258052). Str9
CC performs epoxidation of the 2,3 olefin of prestrobilutin A, followed by
CC Meinwald rearrangement to furnish the aldehyde intermediate (Probable).
CC Rapid enolization of the aldehyde intermediate would give the beta-
CC methoxyacrylate skeleton and methylations catalyzed by str2 and str3
CC complete the synthesis and lead to the production of strobilurin A
CC (Probable). The short-chain dehydrogenase stl2 and the dehydrogenase
CC str4 play a role in the shunt pathway leading to the production of
CC bolineol (PubMed:30258052). The cluster encodes no obvious halogenase
CC gene that could be involved in production of strobilurin B, nor any
CC obvious dimethylallyl-transferase that could be involved in the
CC production of strobilurin G (Probable). It is possible that unknown
CC proteins encoded in, or near, the cluster (such as str1 or stl1) may
CC form new classes of halogenases or dimethylally-transferases, or that
CC the responsible genes are located elsewhere on the genome (Probable).
CC Similarly, proteins encoded by str5/str6 hydrolases appear to have no
CC chemical role in the biosynthesis of strobilurin A (Probable). Finally,
CC no obvious self-resistance gene is found within the cluster (Probable).
CC {ECO:0000269|PubMed:30258052, ECO:0000305|PubMed:30258052}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:30258052}.
CC -!- INDUCTION: Induced in strobilurin-producing conditions (on CGC medium
CC after 6 days of growth). {ECO:0000269|PubMed:30258052}.
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; 2 methyltransferase
CC (CMeT) domains 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 (Probable).
CC Very unusually, the ACP is followed by a thiolesterase (TE) domain that
CC may be responsible for release of prestrobilurin A (Probable). The CMeT
CC domain located between the DH and KR domains is probably inactive due
CC to mutations in the SAM-binding motif, as is the ER, which is more
CC similar to the inactive ER domain of tenellin synthetase (TENS)
CC (Probable). The C-terminal CMeT domain is likely to be active, as the
CC SAM-binding site appears to be intact and probably attaches the C-4
CC methyl group (Probable). {ECO:0000305|PubMed:30258052}.
CC -!- BIOTECHNOLOGY: The structure of strobilurin A was used for the
CC development of the major class of beta-methoxyacrylate agricultural
CC fungicides since its beta-methoxyacrylate toxophore targets the Qo site
CC of complex III of the mitochondrial electron transport chain and
CC prevents adenosine triphosphate synthesis (PubMed:563391,
CC PubMed:6271595). Compounds such as azoxystrobin (Syngenta) and Kresoxim
CC methyl (BASF) are among the most widely used fungicides worldwide
CC (PubMed:12146165, PubMed:29711574). This class of antifungals are used
CC as effective treatments against a broad range of destructive fungal
CC plant pathogens and make significant contributions to food security
CC (PubMed:12146165, PubMed:29711574). The strobilurin fungicides are
CC estimated to have been worth 3.4 billion dollars in 2015 and they make
CC up 25% of the fungicide market and 6.7% of the total crop protection
CC market (PubMed:30258052). {ECO:0000269|PubMed:563391,
CC ECO:0000269|PubMed:6271595, ECO:0000303|PubMed:12146165,
CC ECO:0000303|PubMed:29711574, ECO:0000303|PubMed:30258052}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; KY070339; ATV82110.1; -; Genomic_DNA.
DR SMR; A0A384XH94; -.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0004312; F:fatty acid synthase activity; IEA:TreeGrafter.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0004435; F:phosphatidylinositol phospholipase C activity; IEA:InterPro.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR GO; GO:0035556; P:intracellular signal transduction; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0046189; P:phenol-containing compound biosynthetic process; IEA:UniProt.
DR GO; GO:0030639; P:polyketide biosynthetic process; IEA:UniProt.
DR GO; GO:0009403; P:toxin biosynthetic process; IEA:UniProt.
DR CDD; cd02440; AdoMet_MTases; 1.
DR CDD; cd00833; PKS; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.40.50.1820; alpha/beta hydrolase; 1.
DR Gene3D; 3.40.366.10; Malonyl-Coenzyme A Acyl Carrier Protein, domain 2; 1.
DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1.
DR Gene3D; 3.10.129.110; Polyketide synthase dehydratase; 1.
DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 2.
DR InterPro; IPR029058; AB_hydrolase_fold.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR014043; Acyl_transferase_dom.
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; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR020807; PKS_DH.
DR InterPro; IPR049551; PKS_DH_C.
DR InterPro; IPR013968; PKS_KR.
DR InterPro; IPR049900; PKS_mFAS_DH.
DR InterPro; IPR050091; PKS_NRPS_Biosynth_Enz.
DR InterPro; IPR001711; PLipase_C_Pinositol-sp_Y.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR001031; Thioesterase.
DR InterPro; IPR016039; Thiolase-like.
DR PANTHER; PTHR43775; FATTY ACID SYNTHASE; 1.
DR PANTHER; PTHR43775:SF37; FATTY ACID SYNTHASE; 1.
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; PF13489; Methyltransf_23; 1.
DR Pfam; PF14765; PS-DH; 1.
DR Pfam; PF00975; Thioesterase; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00822; PKS_KR; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SUPFAM; SSF53474; alpha/beta-Hydrolases; 1.
DR SUPFAM; SSF52151; FabD/lysophospholipase-like; 1.
DR SUPFAM; SSF50129; GroES-like; 1.
DR SUPFAM; SSF51735; NAD(P)-binding Rossmann-fold domains; 1.
DR SUPFAM; SSF55048; Probable ACP-binding domain of malonyl-CoA ACP transacylase; 1.
DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 2.
DR SUPFAM; SSF53901; Thiolase-like; 1.
DR PROSITE; PS00606; KS3_1; 1.
DR PROSITE; PS52004; KS3_2; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
DR PROSITE; PS52019; PKS_MFAS_DH; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Methyltransferase; Multifunctional enzyme; NADP;
KW Oxidoreductase; Phosphopantetheine; Phosphoprotein;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..2824
FT /note="Highly reducing polyketide synthase stpks1"
FT /id="PRO_0000449327"
FT DOMAIN 8..428
FT /note="Ketosynthase family 3 (KS3)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348,
FT ECO:0000305|PubMed:30258052"
FT DOMAIN 886..1168
FT /note="PKS/mFAS DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT DOMAIN 2109..2196
FT /note="Carrier"
FT /evidence="ECO:0000305|PubMed:30258052"
FT REGION 517..854
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30258052"
FT REGION 886..1004
FT /note="N-terminal hotdog fold"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT REGION 894..1083
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30258052"
FT REGION 1018..1168
FT /note="C-terminal hotdog fold"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT REGION 1101..1449
FT /note="Methyltransferase (CMet) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30258052"
FT REGION 1213..1232
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1518..1840
FT /note="Enoyl reductase (ER) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30258052"
FT REGION 1842..2096
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30258052"
FT REGION 2200..2414
FT /note="Thioesterase (TE) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30258052"
FT REGION 2608..2809
FT /note="Methyltransferase (CMet) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30258052"
FT ACT_SITE 177
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 312
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 348
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 616
FT /note="For malonyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 925
FT /note="Proton acceptor; for dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT ACT_SITE 1078
FT /note="Proton donor; for dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
SQ SEQUENCE 2824 AA; 306372 MW; 4A5CE09DBB7DDD85 CRC64;
MSPTAEIPKP VAVVGISAEF PSGTLSDANF DHQSFFDFLL SGKDAVERIP KDRFNIDGWQ
GSHLGQILPE DACFLKNVHL FDHFEFGISS KDALTMGAGT RKLVEHSFLA LLDSGINCRS
QNVAAFSSAV AFDLLSAADA DEFEPRDGFG GGAAAVANRI SYQLDLLGPS IPVDTACSSS
LMALHLGVQS LRAGECEAAV IGGSQINHRF LDWIFYSQLS ILSPGGKSIP FDSSADGFGR
GEAVVVLVVK LLEDAIRDGD KIYATVLNTA VNSTGSAGPV KTPIAESQAA AMLTAYKGIG
RSPSEADFIE CHATGTSVGD PVEANWVGNH FKRDSELLIG SVKGNVGHTE ITSFLTSFSK
VISMFDTNRI PPQANFKEPN PAIHWEEYNM RTPTQIEGFT TRNPSGKRLA SINASGLLGA
NGHVIAESPP PKAAKPSALP TGMPVLLMAA GLSPRSTTAI AADLSKLASE IPDELPILSN
IFGRRARQLT WRAAAISTSD GPFVFPAPRF VPRGTPQLVF VFSGQGPQHI EMGRQLFKYY
PVFRDSILKM DKVHVELTGK SIVKDLGFFG ETRSSTALPD VWPVGLTVPS IAMIQMALVD
LLAAFGIRPN LVFGHSAGEA AMSYTSGALP QELAMEIAVR RSQAMSIVEG SGGMAAVSCA
PSVAREIVQE VLDEAGPDSG VLEIGCFNAP EAFTISGTHA LLDKAVAIAS GRGLFARKIK
ARVPGHCTLM EPCKERYVEQ MEVAFSRYPG AHVPVVPTFS TQTGARWESE FTPEYMWNNG
RVPVQFEQTV TAVVQEMPEA IFVEIGPHPA LSSYISGMGA KPDKVVCPMR RVKNVTGFNE
IFELLTAVGN LSTLGVNTIN FHAVNATDCL EISKPIPAYP FAPKTMPFYS ESSELAVKMK
RSRKGPLNYD TLAVNALTHP DLAEHVIKGE PILPATGFFE MIFEEGARTI WDIELRSLLP
LLPEKVLNVN VKSDGHAWSI VSSSGGRNPR LHATGFMTTE VMDKDAGPID LAAIRARTTP
ADISNLYAIL NNTAAFGPLY RRIEACYEGD HEILYQVRGN APELTAHYNY VFHPSLLDSC
IHGLLHPVFT GNADKSVFYL PSHIGRVTLY DRAIEEAVPE TLYSYVVPHD WTPDSIACDA
FIVNERGERL VTLIDCVLSK HWTGAVPTRP DTSYEYIYQP LGLPAAELVK SEAQQQDYAF
LDAIVAHADE KVAPPSANGH ANGHANGSAN GSAVGTVGED RKVFEEIVQS IASDELELKA
SSILGLFSAS LDAPVAAVRQ ILDHAAKSGK QVVRILDIGD ATASLYKQIN AFASEYPSLR
VDYTACGHEH ATLDLRLASY NVDNVSKQAG LSPSTYDVII ETHTLGFAAE LDRSLEYLHG
LLLPGGFLVA LEANGSAQAS GGKWIDQVFS PQGRWSGLRS GKQHHRLSQS EWSGQLQKAK
FQVVDGAQDA ENTLFLTLLA QKHSLSTVSA SSAASSAKVE EPAVFSFDHS RVLDLQKTVL
ASMSSGASNT KLWIESTTGT FDGAVATGFA RSLMRELVAV DVRLVLFDPA WKAESRIPAI
RQLSTLPSLE SEIVLDASGV VMVPRLRSYA PRAPDSLDTT KYWVVDETKT VVQPAQPLPG
PHQVLVKISS LSEAEGGLRG IVGTVARSGS SQWPVGAHVV TVAPSALSNF TLVHEGQLAQ
APQTADEHST AKVALLLVFA ALGLRLDSRP LQSLQQIKVV VIHTGTVASS LARLLEYLGV
KPVLVAPSLP LLLPRLSPGD VIIGGLSAAF ARTVPRINGV SVFNWEDPEQ GALAAVAQNP
WLVGTTVDAH LARALPQVSV EGSSLTPDQL LPSDFSVSQS LALADDKTYL VLGGIGSLGL
QIAIWMYQKG ARHIVLTSRT GVSRLAGTKN RSLRGAVEYL KTLPDLELRL EPCDASSEES
LSKLISSLDR PLAGAMLTAA VMADGLFLKQ SADTYPIPFK PKTDAYFAFE KVVDIKKLDF
LLAVSSVAGF GAAGQTNYAS ANTGIEYLTA RYPNAWSFVA PGIADSNVGF DLFTSTNSHL
EQWESSTMNS YEICLCLEDG LLRMANNERI SIYVPNLNWD AISQSVSESV LYNHLVKLDA
ATDELEVEDP YEVLQEIVLK FVDASEEEFE RNVPLTSYGL DSLSAARMST ALKPYLAITQ
IQLLGDLSLD DLVEKMQATK HVAVEETAVS TAEKPFAWDA MHQPGQTILK FNIGSGTPLI
ILHGGAGDTA AFRAIQEQFS TPLWAIQPTP EAPLDTVDTL AQFYFEKIKE ARPAGPYRIA
GFSASSMVTL RLAQLLEANE DEIAQLTFVD HFPLFFTSAI HGFTEDHKTF EDLTAYGRKA
SVALVAECCR RDTATARRLY GENLVAASNG QPSATNAMES WEWIQKTTRM NLKQVVDFGG
GWEAWASSDA TTRMEAARRR MVEEIAKVKA PMNVMIANWG IRALINSEWT DLGISRGGRE
VRTQYYDAGH FDIFEKPDFS RNLEFDWVDP HPVHQLATMI HNPAMNDLRA LFKILDTKAL
QVMADTISQN PVVGSEISRQ RLFEVCKEFV RTQKHSTWTD EEYEHSKALF PTYFETTERI
SKVHPSIMES PAAAVGALYS DDMIDGFYRQ NKVFTSMNQE AAKTFKALVS SPDFGKQRPI
RVLEVGAGVG GLTKFLVEAL CDMPNADVEY TVTDLSYTLA SSLAESFSYK NMVAKMYDLS
KKPSEQGLQL GHYDVITGLN VIHAVPDLNA TLTDLHSLLA PGGRILIVDT DGTARTSNPP
RPGAIWNDFI WGSFQGWFGY TDDRTHCTID EDEWRKRLTA TGYSNVQVCH EDAGTCILFE
AEKV
//
