PHM1_PYRSX
ID PHM1_PYRSX Reviewed; 3961 AA.
AC A0A2Z5XAL7;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 10-OCT-2018, sequence version 1.
DT 03-AUG-2022, entry version 18.
DE RecName: Full=Hybrid PKS-NRPS synthetase phm1 {ECO:0000303|PubMed:29972614};
DE Short=PKS-NRPS phm1 {ECO:0000303|PubMed:29972614};
DE EC=2.3.1.- {ECO:0000269|PubMed:29972614};
DE EC=6.3.2.- {ECO:0000269|PubMed:29972614};
DE AltName: Full=Phomasetin biosynthesis cluster protein 1 {ECO:0000303|PubMed:29972614};
GN Name=phm1 {ECO:0000303|PubMed:29972614};
OS Pyrenochaetopsis sp.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Dothideomycetes;
OC Pleosporomycetidae; Pleosporales; Pleosporineae; Pyrenochaetopsidaceae;
OC Pyrenochaetopsis; unclassified Pyrenochaetopsis.
OX NCBI_TaxID=1756125;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, CATALYTIC ACTIVITY, DISRUPTION
RP PHENOTYPE, DOMAIN, AND PATHWAY.
RC STRAIN=RK10-F058;
RX PubMed=29972614; DOI=10.1002/anie.201805050;
RA Kato N., Nogawa T., Takita R., Kinugasa K., Kanai M., Uchiyama M.,
RA Osada H., Takahashi S.;
RT "Control of the stereochemical course of [4+2] cycloaddition during trans-
RT decalin formation by Fsa2-family enzymes.";
RL Angew. Chem. Int. Ed. 57:9754-9758(2018).
RN [2]
RP FUNCTION.
RX PubMed=34121297; DOI=10.1002/anie.202106186;
RA Fujiyama K., Kato N., Re S., Kinugasa K., Watanabe K., Takita R.,
RA Nogawa T., Hino T., Osada H., Sugita Y., Takahashi S., Nagano S.;
RT "Molecular basis for two stereoselective Diels-Alderases that produce
RT decalin skeletons*.";
RL Angew. Chem. Int. Ed. 60:22401-22410(2021).
CC -!- FUNCTION: Hybrid PKS-NRPS synthetase; part of the gene cluster that
CC mediates the biosynthesis of the trans-fused decalin-containing
CC tetramic acid phomasetin, the stereochemical opposite of the HIV-1
CC integrase inhibitor equisetin (PubMed:29972614). The PKS module of phm1
CC together with the enoylreductase phm4 catalyze the formation of the
CC polyketide unit which is then conjugated to L-serine by the
CC condensation domain of the phm1 NRPS module (PubMed:29972614). Activity
CC of the Dieckmann cyclase domain (RED) of phm1 results in release of the
CC Dieckmann product intermediate (PubMed:29972614). The Diels-Alderase
CC phm7 then uses the Dieckmann product of phm1 as substrate and catalyzes
CC the Diels-Alder cycloaddition to form the decalin ring of N-
CC desmethylphomasetin (PubMed:29972614, PubMed:34121297). N-
CC desmethylphomasetin is further methylated to phomasetin by the
CC methyltransferase phm5 (PubMed:29972614). {ECO:0000269|PubMed:29972614,
CC ECO:0000269|PubMed:34121297}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:29972614}.
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. Thus, an NRP synthetase is generally composed of one
CC or more modules and can terminate in a thioesterase domain (TE) that
CC releases the newly synthesized peptide from the enzyme. Occasionally,
CC epimerase (E) domains (responsible for L- to D- amino acid conversion)
CC are present within the NRP synthetase. CcsA contains also a polyketide
CC synthase module (PKS) consisting of several catalytic domains including
CC a ketoacyl synthase domain (KS), an acyl transferase domain (AT), a
CC dehydratase domain (DH), a methyltransferase domain (MT), and a
CC ketoreductase domain (KR). Instead of a thioesterase domain (TE), phm1
CC finishes with a reductase-like domain (R) for peptide release. Phm1 has
CC the following architecture: KS-MAT-DH-MT-KR-PCP-C-A-T-R.
CC {ECO:0000305|PubMed:29972614}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of phomasetin
CC (PubMed:29972614). Phm7 are involved in control of the stereochemistry
CC at C3 and C6 during trans-decalin formation (PubMed:29972614).
CC {ECO:0000269|PubMed:29972614}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the NRP synthetase
CC family. {ECO:0000305}.
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DR EMBL; LC361337; BBC43184.1; -; Genomic_DNA.
DR SMR; A0A2Z5XAL7; -.
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; 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; 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 TIGRFAMs; TIGR01733; AA-adenyl-dom; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 2.
PE 1: Evidence at protein level;
KW Ligase; Methyltransferase; Multifunctional enzyme; Oxidoreductase;
KW Phosphopantetheine; Phosphoprotein; Repeat; Transferase.
FT CHAIN 1..3961
FT /note="Hybrid PKS-NRPS synthetase phm1"
FT /id="PRO_0000453334"
FT DOMAIN 2386..2464
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 3542..3616
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 7..439
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 541..867
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 933..1234
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000255"
FT REGION 1376..1569
FT /note="Methyltransferase (MT) domain"
FT /evidence="ECO:0000255"
FT REGION 2106..2277
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255"
FT REGION 2482..2527
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2553..2993
FT /note="Condensation (C) domain"
FT /evidence="ECO:0000255"
FT REGION 3019..3424
FT /note="Adenylation (A) (KR) domain"
FT /evidence="ECO:0000255"
FT REGION 3725..3871
FT /note="Reductase (RED) domain"
FT /evidence="ECO:0000255"
FT ACT_SITE 178
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2424
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3576
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 3961 AA; 434821 MW; 3A6487C131E32B26 CRC64;
MTSSEPIAII GSACRFPGGA DTPSKLWELL KEPRDLLQKV PEKRRWHSEA FYHKDPEHHG
TSNVSSSYFL DDDPASFDNT FFNIQPSECE AIDPQQRMLM ETVYDSVCSA GQTIDGLRGS
STAVYVGMMC DDWSAILTKD AESIPQYSAT GMGRSIMSNR ISYFFDWHGP SITLDTACSS
SLVAVHLAVQ ALRNGDCGTA IAAGVNLCLS PGMYIATSNL HMLSEGARSR MWDKDVDGYA
RGEGIASVVL KPLSAAIRDG DHIECLIRAT GVNQDGKTQG LTMPSATAQT ALIRQTYERA
GLDIEKPEDR PQFFHAHGTG TPAGDPQEAE AISTAFYSGG LSDKLYVGSI KTVIGHTEGT
AGLASLIGTS LALQHGVIPP NLLFNELNPR LIPFYNNLEV PTSAKPWPQL LPGQARRASV
NSFGFGGTNA HAIVEAYEPP TSSGAADNVF APLVFSAATE KSLRASLSAH GDYLQANPQV
PLRNFAYTLQ ERRSTLAFRA VIPASNTTDA VERINALLDD ADSVELGTKH FATPHPRLLG
VFTGQGAQWP RMGAQIVEAS PYASKKLGEL DTALATLPPD VRPSWTLREE ILADLEVSKV
AEAAISQPLC TAVQILLVDL LTAAGIRFDA VVGHSSGEIG AAYAAGFISA ETAIRVAYLR
GFYAKLAGAA EMKGSMMAVG TSYEDALEFC QLEHFMGRIS VAAVNSDSSI TLSGNEDAIM
EAVEIFKDEG KFARQLKVDT AYHSVHMLPC SEPYLKAMES VTQSTAPRDN TAGPRPTWYS
SVLDGAVMGP GEVNSEYWVS NMVNPVLFSA AVAAAVSATG PFNLALEVGP HPALKGPCLD
TLAAASGDSI PYSGLLSRSK NDILELSSAL GFVWANLGAS SVRFGDFEKL ISGVSENPRP
VKDLPKYAFD HTRSFWQISR ASGAQFLAQD PPHPILGKRC LERETSQHVE WRNILSPKEL
PWLQGHRIQG GMVFPAAGYV AMAIEAMKIA VGKSRMSLIH IENLHIGRAM AFNQETSTME
CLFRLNIVNS SPDSMKAKFS CCSGAPYETG TTMVLNAEGT VTVTLAEPEP DAIPYMKPKN
FNMTEIEVDR FYTQIHKLGY EYSAPFRGML SIQRKNAYAL GTMEDQGGSD WEDQLLVHPG
MLDTAIQSSS AAFGCPGDGM MWTLYIPTGI QSIIINPYYT TYATEKQEVL PWETISRGMV
NTRTSMDINI FSQDNAHTFI QVEGLELVPF TAARPEDDAN IFSSLEYRID SPSGDLAVIN
DGWDSHSSEA AIKGERVSFF YLRRLLEEIT PEEKEKTLPH YRHLLNWAAH VVARVSAGKN
PCVPASCMQD TQEIIDSMWD GVRNRADIRL IESVGRNLIK VVREGSGILE HMDGLFDFYD
QGLGLDRANR HLARMVGQLA HRYPHMNIFE IGAGTGGSTR NILSAIREEF STYTYTDVSS
GFFEAAQELF QDYEDRMIYS TYNMEHEPTS QGFEEGHYDL LLASNVLHAT DKLEEMMLSA
RKLLKPGGYL IALELTNNDS MRVGLPMGTL PGWWLGAETG RPWGPTVTLP QWDSLLRKCG
FGGIDTSTPI QHRLQASTIF AAQAVDDRVN LLRNPLSLVN NLPLTDAPRL VIIGGESLAT
HAIANNISSL LASHYSEIVR IVSFADLDLD VLPYGTAVLS LADLDEPVFK DISPAKLDAL
KTLWRQAFNI VWVTQGARAA EPYSSMMIGL GRAMIHEYPT ISLQLMDIDT IADESRATQL
IAKEFIRLEL LNTFKRGTKS NLDLLWSIES EVTFEGSARL IPRLYLNKEA NARYNSARRS
IETQVNWKAS LVTVALQGDT YGLSKPSPLR LPISQPSDTK VTSLNVSHFL LQGLKIDGLN
PLVLCAGTER STGKHLLALS HSLESQPEIQ TKWSAPLPSG SDPSQIIAAV AAEIIADQIT
KLHTRSGIMI IHEATEQLAV ALHTRAQTLG CQIVFTTSSK DHAQRGWQFI PQNISRRLIK
RTLPADSNVF IDLSYSSASV AAGRLISGSV SKSCAKYTSD AFYSASVSSE FDLESSTKVE
EAFQQAYDSV TQSKTGLVDP ITIPIQEIGD VSVSQKPLAV VVSSATNLAV KVEAIDSGVI
FRQDKTYLLI GMSGQVGQSL CQWMVKCGAR HVVLTSRRPL VHDDFIESMK DLGANVRTFA
LDITQRESLH KCYEEIVATM PPIAGVANGA MILRDSMFDG MTFQNLTTVL EPKVAGTRYL
DELFYDAPLD FFIVLSSITS LVGNSSQSNY TAANMFMVAL VEQRRKRGVP GSAISISALI
GIGYVENSEF TGEYFENIGL RNISEQDLHQ QFAEAILAGR PETQGSSEVA IGLIPFYPER
DDKAQFHTDI KFNHLMLERK DAQIHGGKGS ALPVRVQLAE AKTKDQAATI IKDGFMVRLK
RTLMIGLDEV VNEKVPLVEQ GIDSLMAVEI RAWFLKELDV DIPVLKVLGG SNITELLQEA
MDRTPSTIID FSSLSNAKAA APVTNTATPP PEVQVTGSAS DSSRSLTPDG LSTSRPSTPV
RTPMTEINDP TPSFSLLSVA PDIAPKVPES VSPMSYGQAR FWFLSDYLED KTSFNMTVMF
KLTGRLQVPR LERAVRTIAH RHDALRTRFF WGGEGDKRIA MQGISAESSI ELEHVRINSE
ADAKNELRKM HEFVWDLDSH QAARMVLLTI NENEHYFMTS GHHISWDGYG FTVLFIDLDA
AYRGEPLSPN GPETQYPAFA AWQRDTYAAG AMKKSIDEYY RPMIDPEARP LPLFPFARAP
NRPLLDHFEQ FEAKVTLQPH VVSKLKQVSR KNGATMFHLY LAALQALVFR LLPEEQSFYL
GVADANRLDK NFMGSLGFFL NLLPVRFDRT APGTKSSDMI KDTRNKAYKA LENSFVPWDV
LLHELKIPRT NTEAPIFQLF VDYRQIVRER AQWCGCSMSD EDWLNARNGY DLTLGITDNP
TGESLLSLRF QKKLYSEEST EMFLRSYVNV LEALASGKDL LVDDLPRWAG ADVEEALNVG
RGPQLELEWP VTVSHRIDQM IGTYASKPAL QDEHNNCMSY EQMGHRINTI AAALIQAGTT
TGTPVGVFQT PSSDWICSML AIFRVGATYI PLDLRNSVAR VSFIVEIAQP LILLTDRETT
LHVAEIQASN ATEIIIPDLS TTTMPLSMEN QARPDSPAVT LFTSGTTGRP KGVVLTHANL
RAQCEGYSRM VNLQSMTSVV LQQTNYNFDV SLDQIFAALA EGGCLYVVPA SKRGDPQAIT
KIMAEKGVTY TVATPSEYET WFRYAPETLA ECKSWGYAFG GGEHLNNGLI GEFAALSTRH
IPELRLFNNY GPTEASLAIT KGEVDFKRPD LEKHVPAGMT IPNYAVAIVD ENLKPVPLET
VGEIVAGGPG VAAGYLGQAD LTREKFISGH DVHRLAAQHS DRWYRTGDRG YLRPDGALFV
HGRILGDTQV KIRGFRVELQ EIENVVLETA KGALTHAVVS LRGTGEDKFL TAHVVFAPDF
AMHLRQDLIR HLEAALPLPS YMQPTVIVPL TKVPVTTNFK IDRNAIQAMP LPQAVAGTDN
LANMEGRVAA LWRIIIPHLT QELTPESDFF AVGGNSILLV KLQAAIKREL QSSPQLIDLI
NSSSLEGMAR HVRAAFINRI DWDLETAVPA DLKEDLEVLT SQPRKHGQDD LTVVITGSTG
YLGRHVLAHL VDSSNVRQII CLVRPEHLQT ASPLSTSSKI RLVAADISQP SLGLGAQTFA
ELAQITDIVF HCAANRSFWD GFESLRHVNF DAAKELARLC VANDAVLHFM SSGAVSKYND
ISPPTDGSDG YIASKWAAEE FLRRVAKFGL RVQVHRPLAL PSEKVSSLSQ EDLKRVQDEL
PRLIAQIGQR PEFSAIHGHI DVRPVSDVAT TLVEDMLVSS VQESGNEATV KNHAAHLRLQ
IKTFAEQIDA DEELSKLPTM DALQWFGAAK RAGFGWLIGA MEMHIEGDDQ SGTTTQVLVQ
R
