PRLS_FUNXX
ID PRLS_FUNXX Reviewed; 4037 AA.
AC A0A089FSA4;
DT 30-AUG-2017, integrated into UniProtKB/Swiss-Prot.
DT 26-NOV-2014, sequence version 1.
DT 03-AUG-2022, entry version 35.
DE RecName: Full=Hybrid PKS-NRPS synthetase prlS {ECO:0000303|PubMed:25226362};
DE EC=2.3.1.- {ECO:0000305|PubMed:25226362};
DE EC=6.3.2.- {ECO:0000305|PubMed:25226362};
DE AltName: Full=Pyrrolocin biosynthesis protein S {ECO:0000303|PubMed:25226362};
GN Name=prlS {ECO:0000303|PubMed:25226362};
OS Fungal sp. (strain NRRL 50135).
OC Eukaryota; Fungi.
OX NCBI_TaxID=1547289;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND PATHWAY.
RX PubMed=25226362; DOI=10.1021/sb500296p;
RA Kakule T.B., Jadulco R.C., Koch M., Janso J.E., Barrows L.R., Schmidt E.W.;
RT "Native promoter strategy for high-yielding synthesis and engineering of
RT fungal secondary metabolites.";
RL ACS Synth. Biol. 4:625-633(2015).
RN [2]
RP FUNCTION.
RX PubMed=25351193; DOI=10.1021/np500617u;
RA Jadulco R.C., Koch M., Kakule T.B., Schmidt E.W., Orendt A., He H.,
RA Janso J.E., Carter G.T., Larson E.C., Pond C., Matainaho T.K.,
RA Barrows L.R.;
RT "Isolation of pyrrolocins A-C: cis- and trans-decalin tetramic acid
RT antibiotics from an endophytic fungal-derived pathway.";
RL J. Nat. Prod. 77:2537-2544(2014).
CC -!- FUNCTION: Hybrid PKS-NRPS synthetase; part of the gene cluster that
CC mediates the biosynthesis of pyrrolocin, a bright yellow trans-fused
CC decalin-containing tetramic acid with antimicrobial activity
CC (PubMed:25226362, PubMed:25351193). The PKS module of prlS together
CC with the enoylreductase prlC catalyze the formation of the polyketide
CC unit which is then conjugated to L-serine by the condensation domain of
CC the prlS NRPS module (PubMed:25226362). Diels-Alderase gNR600 is
CC involved in endo-selective Diels-Alder cycloaddition to form the
CC decalin ring (By similarity). Subsequent methylation is carried leads
CC to pyrrolocin A (PubMed:25226362). The methyltransferase involved in
CC that last step has not been identified yet and is probably located
CC outside of the prl cluster (PubMed:25226362).
CC {ECO:0000250|UniProtKB:A0A0E4AZP0, ECO:0000269|PubMed:25226362,
CC ECO:0000269|PubMed:25351193}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:25226362}.
CC -!- DOMAIN: NRP synthetases are composed of discrete domains (adenylation
CC (A), thiolation (T) or peptidyl carrier protein (PCP) and condensation
CC (C) domains) which when grouped together are referred to as a single
CC module. Each module is responsible for the recognition (via the A
CC domain) and incorporation of a single amino acid into the growing
CC peptide product (By similarity). Thus, an NRP synthetase is generally
CC composed of one or more modules and can terminate in a thioesterase
CC domain (TE) that releases the newly synthesized peptide from the enzyme
CC (By similarity). Occasionally, epimerase (E) domains (responsible for
CC l- to d-amino acid conversion) are present within the NRP synthetase
CC (By similarity). PrlS contains also a polyketide synthase module (PKS)
CC consisting of several catalytic domains including a ketoacyl synthase
CC domain (KS), an acyl transferase domain (AT), a dehydratase domain
CC (DH), a methyltransferase domain (MT), and a ketoreductase domain (KR)
CC (By similarity). Instead of a thioesterase domain (TE), prlS finishes
CC with a reductase-like domain (R) for peptide release (By similarity).
CC PrlS has the following architecture: KS-AT-DH-KR-PCP-C-A-T-R (By
CC similarity). {ECO:0000250|UniProtKB:Q4WAZ9, ECO:0000255}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the NRP synthetase
CC family. {ECO:0000305}.
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DR EMBL; KM107910; AIP87510.1; -; Genomic_DNA.
DR SMR; A0A089FSA4; -.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase 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: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; -; 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; 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; 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; 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; 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; 3.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 2.
PE 3: Inferred from homology;
KW Ligase; Methyltransferase; Multifunctional enzyme; Oxidoreductase;
KW Phosphopantetheine; Phosphoprotein; Repeat; Transferase.
FT CHAIN 1..4037
FT /note="Hybrid PKS-NRPS synthetase prlS"
FT /id="PRO_0000441291"
FT DOMAIN 2447..2522
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 3610..3687
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 7..445
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25226362"
FT REGION 557..879
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25226362"
FT REGION 950..1251
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25226362"
FT REGION 1448..1610
FT /note="Methyltransferase (MT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25226362"
FT REGION 2144..2315
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25226362"
FT REGION 2535..2594
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2614..3046
FT /note="Condensation (C) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25226362"
FT REGION 3094..3495
FT /note="Adenylation (A) (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25226362"
FT REGION 3724..3961
FT /note="Reductase (RED) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:25226362"
FT REGION 3894..3915
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2556..2586
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 178
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2482
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3647
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 4037 AA; 442186 MW; E1E3CAB6E99C85F0 CRC64;
MSSTEPIAVI GSACRFPGSS DRPSKLWELL REPRDLLQKV SERRRWHPDA FYHSDPEHHG
TTNVRSSYFL DEDPADFDNA FFNIQPSEAE AIDPQQRMLM ETVYDSLCSA GQTIEGLRGS
STAVIVGTMC DDWSGVLYKD WETIPQYSAT GMGRSIMSNR VSYFFDWHGP SMTLDTACSS
SLVAVHLAIQ ALRTGESRVA VAAGANLLLG PGMYIAEANL HMLSPKGRSA MWDKDVDGYA
RGEGIASVIL KPLSAAIEDG DHIECLIRAT GVNQDGRTQG LTMPSATAQA ALIRETYARA
GLDIDKPEDR PQFFHAHGTG TPAGDPQEAE AISKAFYSQD ASDSLYVGSI KTVIGHTEGT
AGLASLLGTS LALQHGMVPP NMHFNELNPR IAPFYGNLQV PTTAKPWPKL LPGQPRRASV
NSFVFVIYLD SWLTWPPNAG FGGTNAHAIL EAYEPPSVSP SAGPLFSPLT ISAATEKSLR
ALMSSYSEYL KANPKTSLRD FAYTLQERRS TLAFRAAIAA STSDEAAIKI DGLLDAEDAR
ELSTKHFGIP SPRLLGVFTG QGAQWPRMGA RLVEASPFVA TRLDELDASL ASLPESIRPE
WTLKEQMLED AATSRVAEAA VSQPLCTAVQ ILLVDLLSVA GVRFHAVVGH SSGEIGAAYA
AGLLSASSAI RIAYLRGLYA KLANSPNGNI RGAMMAAGTS FEDASEFCQL EGFEGRIQVA
AVNSASSITL SGDEDAIAEA VEIFKDEGKF ARQLKVDTAY HSAHMLPCSK PYLKSLEAMT
DVLGADASGE GKPAWYSSVH EGEIMKPAAL NPQYWVSNMT NTVLFAPAVA AAVAQSGPFD
MALELGPHPA LKGPCLDTLA EALGDRIPYS GLLSRGQDDI SEMSAALGSV WSNLGAGSVS
FETFEKSISG DLKGRNLIAD LPKYEFDHSR SFWTISRAVG AQLVAHDPPH PVLGRRCVDR
ETSREIQWRN ILSPKEVPWL KGHRIQGGIV YPAAGFVAMA VEAMRALAGK SSINLIKIDN
LFIGRAIAFN EETSTVETLF SVKVVSSSDE SIQASFSCYS GAPHEPGTSM GLNAEGIVTV
TLADHEADVI LFVEPKDFNM TEIETDRFYD QFQRLEYEYS PPFRGMLAIK RKKGHARGTI
EDQSGSDWED QFLIHPGMLD TAFQSSSAAF SCPGDGMMWG LYIPAGIQSI VINPYFTPAG
MGKQQTLPWE AIARSMHKAR STMDINIFSQ DSTHTFIQVE GLELMPFTAA RPEDDAVIFS
RFDYKIDGPS GDIAVADDGF TAEALENAIK GERVSFYYLR RLVESITPEE KANAPRYYRH
LLDWASHVVD RVKSGKNPFV QSSWQLDTEE QIKAIWDKYG DRVDVRLIES VGKHLPDVIR
KGTSILEHME GLFEFYDQGL GLDMANRHLA RMVAQVGHRY PQMRVFEIGE PRKPAPMLLC
CHSDSRVLGA GTGGSTRTIL SYLGDMFSSY TYTDISSGFF EAAQDRFKDF ESRMVYKTFD
MERDPESQGF VEGSYDLVLA SNCLHATDKL EEMMTNARRL LRPGGYLIAL ELTSNETMRV
GLPMGSLPGW WVGAESGRPW GPTVTLPQWD SLLRKCGFGG IDTSTPLLHK LHVSTVFAAQ
AVDDRVSLLR SPLASITVLP PTDAPRLVVV GGEALATHRI AERVASLLGP RFSDIARVTS
FESLDIDALP YGSTVLSLSE LDEPLFKNMN PAKLDALKTL WRQAGKILWV TRGARAEEPF
SSMMLGLGRA MTHEYPNISL QILDLDRLED EEKTAQLFTA ELLRLEVLKK WQHEAQGEVD
FLWSIEPEVC FEGGARLIPR LYKCRPANDR YNSARRPVMT EIDPRETPIL FASEGASYEL
QHPSPLRIPS APPAVSKTRT VNVSHFLLQT VHMSSAGRFM LFAGADRYTG ERLLGLSHTT
ESQPTVPTEW TFPIASEGTN PAEALSSVYG QIIAREILKM VPKGSSIVVH EPDPSLGAAL
LQQAEACATE VVLTTSRKGS VSSEGRFIPA NLSRRLVKKA LPDSTSLYVD LSHAGESSEA
GKLIGKCLPG SCSTYGSGYF HGTTPELRPG SSSSQLSAIF KAACEAAFEG QCQTAIPDIV
QLQDVPSLRA IGRPLTVVDC VSTATVPVNV QTVDSGMIFR ADKTYFLVGM SGQVGQSLCQ
WMVERGARYV VLTSRHPQVH PEYVKSMEAM GATIRVLPLD ITSRDSLQQC YAEMCKTMPP
VAGVAQGAMV LRDSMFDGLS FENLTAVLDP KVTGTQLLDE LFYDAPLDFF IVMSSLTSVV
GNSGQSNYTA ANMFMVALAE QRRKRGVAGS AIAISSLIGI GYVERSEDFT GDYFEKIGYR
NISEQDLHQL FAEAILVGRP GCRESSEITT GLEPFYPERN AKAQFFDDIR FNHFILERHD
AQNLGGKGSA VPVRVQLAEV KTRDEAAVII KGEANSRKND FETQKADSRT DGFLARLRRT
LMISQDEAVN EKASLVEQGI DSLMAVEVRS WFLKELEVDI PVLKILGGSS ITDLLNEALE
RVPVSVVDLK AMANTKASTP EHRKVSVPPP PSVEVKSSSP GSSSEPQSSP ADSPSRPSTP
LRTPMTEMEE SKTLAPVVVE KPKVYPAAKE EASEMSYGQA RFWFLSGYLE DKTSFNMTVM
FKLTGKLQVA RLESAVRTVA QRHEALRTRF FWSGEGDRRT PMQGVLSESP IQLEHVRIES
EADAQKQLAK MHEYVWDLNS WEAARMVLLT VDDDVHYFMV SGHHISWDGY SFTVLFVDLD
AAYCGRPLAP LGPECQYPAF AAWQRDTYAA GAMKKAIDTY YRPMIDPHAK AIPLFPFAKS
PTRPLLDHFE QFEAKATLQP ALVSKLKQLS RKNGATMFHL YLAALQALVF RLLPEEDDFY
LGVADANRMD KSFMGSLGFF LNLLPVRFDR SQPGTKISEI IKDTRNKAYK ALENSFVPWN
VLLQELKIPR TNTEAPIFQL FVDYRQIARD RAQWCGCALS DEDWLNARNG YDLTLGITDN
PTGESLLSLR FQKKLYSEHS TNLFLRSYVT VLESFATGVD LEVSELPRWA PSDVEATLEA
GKVYRKLMTN PQGPCTQLDW PATVSHRIDE MIHEHTAQPA LKDGLGNSLT YGQMRDRINM
ISAALIAGGA IEGSSIGVFQ NPSADWICSM LAIFRIGATY VPLDLRNSIA RIVSIVADVQ
PTVILSDRYT TTKIRQIGAV QATEIVVSDI ATSVSAPDLP NKAAPDSRAV ILFTSGTTGK
PKGVILTHAN LRAQCEGYSR MVDLPSMVSV VLQQTIYNFD VSLDQIFAAL ADGGCLYVVP
AEKRGDPQAI TEIMAEQGVT YTVATPSEYE IWFRYARDNL ARCKSWGYAF GGGEHLHSGL
IHEFSSLAAQ HIPGLRLFNN YGPTEASLAI TKGEVQHSDP GLEDHVPAGW IIPNYKVAVV
DEKLQPVPFE TSGEILAGGP GVASGYLGQD ELTREKFIAG VRIHPLAAKS ANTWYRTGDR
GRLRRDGALY VDGRILGDSQ VKIRGFRVEL QEIEAVLLEA AKGALSHAVI TARGTGEDRF
LAAHVVFAPD FPQHRRQATI HHLESKLPLP PYMQPTVIVP LASIPVTSNF KLDRKAIQAL
PLPETDGLGE NLADVEKSVA MLWKSIIPHG VRDLTPETNF FDVGGNSILL VKLKAAMSRE
LKVTPLLIDL MNSSTLGGMA RIVRASSGAR VINWEAETSV PESLRALVKQ KKTLSRSKRK
NENLVVVLAG ATGYLGRHIL ARLVNAPEVS EINCLVRDEG LEAATSSLQN SPKVRLIPAD
LSQPDIGLSL AKFSDLSQRA DIVVDCAANR SFWDGYETLR TVNLDAVKEL ARLCVTNGAS
LHFVSSGAVQ AYENSAPPTD GSDGYVASKW AAETFLRRAA ESLGLQVHIH RPLGSADVGA
PDSTPDRKNP STKDEIQRDL DHILLKLGKR PDFSAVTGYV DVTPVNSVVS DMVAAMIQEI
SSGHGGAMLR VTEHRGRLRL HIKEFGDHIG ASSQLSALPT MNPLFWFADA KKAGFAQLIT
SQRLVMHNKE GELVTRR
