PYIS_MAGGR
ID PYIS_MAGGR Reviewed; 4065 AA.
AC A0A4P8WAE5;
DT 22-APR-2020, integrated into UniProtKB/Swiss-Prot.
DT 31-JUL-2019, sequence version 1.
DT 03-AUG-2022, entry version 14.
DE RecName: Full=Polyketide synthase-nonribosomal peptide synthetase pyiS {ECO:0000303|PubMed:31099577};
DE Short=PKS-NRPS pyiS {ECO:0000303|PubMed:31099577};
DE EC=2.3.1.- {ECO:0000305|PubMed:31099577};
DE EC=6.3.2.- {ECO:0000305|PubMed:31099577};
DE AltName: Full=Pyrichalasin H biosynthesis cluster protein A {ECO:0000303|PubMed:31099577};
DE AltName: Full=Pyrichalasin H synthase {ECO:0000303|PubMed:31099577};
GN Name=pyiS {ECO:0000303|PubMed:31099577};
OS Magnaporthe grisea (Crabgrass-specific blast fungus) (Pyricularia grisea).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Sordariomycetidae; Magnaporthales; Pyriculariaceae; Pyricularia.
OX NCBI_TaxID=148305;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DISRUPTION PHENOTYPE, DOMAIN,
RP AND PATHWAY.
RC STRAIN=NI980;
RX PubMed=31099577; DOI=10.1021/acs.orglett.9b01344;
RA Wang C., Hantke V., Cox R.J., Skellam E.;
RT "Targeted gene inactivations expose silent cytochalasans in Magnaporthe
RT grisea NI980.";
RL Org. Lett. 21:4163-4167(2019).
RN [2]
RP FUNCTION.
RX PubMed=31644300; DOI=10.1021/acs.orglett.9b03372;
RA Wang C., Becker K., Pfuetze S., Kuhnert E., Stadler M., Cox R.J.,
RA Skellam E.;
RT "Investigating the function of cryptic cytochalasan cytochrome P450
RT monooxygenases using combinatorial biosynthesis.";
RL Org. Lett. 21:8756-8760(2019).
RN [3]
RP FUNCTION.
RX PubMed=32039410; DOI=10.1039/c9cc09590j;
RA Hantke V., Skellam E.J., Cox R.J.;
RT "Evidence for enzyme catalysed intramolecular [4+2] Diels-Alder cyclization
RT during the biosynthesis of pyrichalasin H.";
RL Chem. Commun. (Camb.) 56:2925-2928(2020).
CC -!- FUNCTION: Hybrid PKS-NRPS synthetase; part of the gene cluster that
CC mediates the biosynthesis of the mycotoxin pyrichalasin H, a tyrosine-
CC derived cytochalasan that inhibits the growth of rice seedlings, but
CC also inhibits lymphocyte capping and actin polymerization and alters
CC cell morphology (PubMed:31099577) (Probable). Pyrichalasin H is
CC indicated as the responsible agent for the genus-specific pathogenicity
CC of M.grisea toward crabgrass (PubMed:31099577). The first step in the
CC pathway is catalyzed by the O-methyltransferase pyiA which methylates
CC free tyrosine to generate the precursor O-methyltyrosine
CC (PubMed:31099577). The hybrid PKS-NRPS pyiS, assisted by the enoyl
CC reductase pyiC, are responsible for fusion of the O-methyltyrosine
CC precursor and the polyketide backbone (PubMed:31099577). The polyketide
CC synthase module (PKS) of pyiS is responsible for the synthesis of the
CC polyketide backbone and the downstream nonribosomal peptide synthetase
CC (NRPS) amidates the carboxyl end of the polyketide with the O-
CC methyltyrosine precursor (PubMed:31099577). As the NRPS A-domain
CC demonstrates substrate tolerance, pyiS can also use phenylalanine,
CC tyrosine and even para-chlorophenylalanine as amino acid precursor,
CC which leads to the production of novel cytochalasans, including
CC halogenated cytochalasans (PubMed:31099577). Because pyiS lacks a
CC designated enoylreductase (ER) domain, the required activity is
CC provided the enoyl reductase pyiC (PubMed:31099577). Reduction by the
CC hydrolyase pyiE leads to 1,5-dihydropyrrolone, which is substrate for
CC dehydration and intra-molecular Diels-Alder cyclization by the Diels-
CC Alderase pyiF to yield the required isoindolone-fused macrocycle
CC (PubMed:32039410). The tailoring cytochrome P450 monooxygenases piyD
CC and piyG catalyze the hydroxylation at C-18 and C-7, respectivily,
CC whereas the short-chain dehydrogenase/reductase pyiH reduces the
CC carbonyl at C-21 in preparation for the transfer of an acetyl group by
CC the acetyltransferase pyiB (PubMed:31099577). These 3 reactions whose
CC order is not clear yet, lead to the production of O-methylpyrichalasin
CC J, a deacetylated pyrichalasin H (PubMed:31099577). Finally, pyiB to
CC converts O-methylpyrichalasin J into the final product pyrichalasin H
CC via acetylation of C-21 (PubMed:31099577).
CC {ECO:0000269|PubMed:31099577, ECO:0000269|PubMed:32039410,
CC ECO:0000305|PubMed:31644300}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:31099577}.
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), pyiS
CC finishes with a reductase-like domain (R) for peptide release. PyiS has
CC the following architecture: KS-AT-DH-MT-KR-PCP-C-A-T-R.
CC {ECO:0000250|UniProtKB:Q4WAZ9, ECO:0000305|PubMed:31099577}.
CC -!- DISRUPTION PHENOTYPE: Results in the complete abolition of pyrichalasin
CC H and deacetylated pyrichalasin H production.
CC {ECO:0000269|PubMed:31099577}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR EMBL; MK801691; QCS37521.1; -; Genomic_DNA.
DR SMR; A0A4P8WAE5; -.
DR Proteomes; UP000515153; Genome assembly.
DR GO; GO:0016746; F:acyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0016853; F:isomerase activity; IEA:UniProtKB-KW.
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; 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; 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; 1.
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 PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS50075; CARRIER; 2.
PE 3: Inferred from homology;
KW Acyltransferase; Isomerase; Ligase; Methyltransferase;
KW Multifunctional enzyme; NADP; Oxidoreductase; Phosphopantetheine;
KW Phosphoprotein; Reference proteome; Repeat; S-adenosyl-L-methionine;
KW Transferase.
FT CHAIN 1..4065
FT /note="Polyketide synthase-nonribosomal peptide synthetase
FT pyiS"
FT /id="PRO_0000449442"
FT DOMAIN 2411..2492
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 3634..3714
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 9..443
FT /note="Ketoacyl synthase (KS) domain"
FT /evidence="ECO:0000250|UniProtKB:A1CLY8, ECO:0000255"
FT REGION 552..875
FT /note="Acyl transferase"
FT /evidence="ECO:0000250|UniProtKB:A1CLY8, ECO:0000255"
FT REGION 951..1254
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000250|UniProtKB:A1CLY8, ECO:0000255"
FT REGION 1409..1593
FT /note="Methyltransferase (MT) domain"
FT /evidence="ECO:0000250|UniProtKB:A1CLY8, ECO:0000255"
FT REGION 2129..2302
FT /note="Ketoreductase (KR)domain"
FT /evidence="ECO:0000250|UniProtKB:A1CLY8, ECO:0000255"
FT REGION 2497..2561
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2645..3076
FT /note="Condensation"
FT /evidence="ECO:0000250|UniProtKB:A1CLY8, ECO:0000255"
FT REGION 3112..3516
FT /note="Adenylation"
FT /evidence="ECO:0000250|UniProtKB:A1CLY8, ECO:0000255"
FT REGION 3760..3975
FT /note="Reductase-like"
FT /evidence="ECO:0000250|UniProtKB:A1CLY8, ECO:0000255"
FT COMPBIAS 2502..2561
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 179
FT /note="For ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2452
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3674
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 4065 AA; 448098 MW; 53853B366CF14C6D CRC64;
MAATFSEPVA IIGTGCRFPG QCNTPSKLWE LLQTPKDLLK EIPENRFSTE AFYHPQNYHH
GTCNVRHSYF LEEDLRGFDA QFFGINPVEA HSVDPQQRLL LETVYESLEA AGLSMKEMQG
SDTAVYVGVM SADFTDMIGR DPETFPTYFA TGTARSILSN RLSFFFDWRG PSMTIDTACS
SSLIEPRTGA NKPDCAEQVA GSNLILGSEQ YIAESKLQML SPTGRSRMWD ADADGYARGE
GVAAIVLKKL SQAIADGDHI ECIIRETGAN QDGRTPGITM PSATAQEALI RTTYKKAGLD
ISKRSDRPQF FEAHGTGTPA GDPIEARAVS NAFFGPRSHF SPTSPDDTLF VGSIKTVVGH
TEGTAGLAAV IKASLALQAG VVPPNMHLSK LNPKIEPFYG NVQILSEARQ WPKLAEGGVR
RVSVNSFGFG GANCHAILEA YEPESTLDRR RYNKRTGKCF TPFLFSAATE NALAAQLDKY
RAHVACGNAS APGDLKKLSL TLSNRRSALP WRAVVPASNS VERLIENLDQ CNDFTNETSA
SSLGTRPRIL GIFTGQGAQW PRMGAALIES SPAAAKILAR LDESLRLLPI RDRPTWSLRE
KILEGAESSS VAMAFISQPV CAAVQIMLVD MLRAAGIEFS GVLGHSSGEI SAAYAAGYLS
SEDAIRAAYY RGFHMKSLTQ KKGAMIAVGT SYDDAKELCD LPAFEGRVCV AASNSPFSVT
LSGDADAIDE VKALMDEEKK FNRLLQVDRA YHSHHMKACA AAYMASLQQC GVRTLTRTAA
SSRCQWVSSV YVRHSAELAA EGGLEAKYWA SNLTMPVMFT EALQKLLGDC KDGKAYDLAI
EVGPHPALKG PAVQTMSEFL GGQSIPYTGV LSRGKDDVES FSTTLGYIWR TLGEGAVDFL
GYSRFMNEEQ GEATITPLNG LPTYPWDHHR KFWHESRLSR AYRFNKDPVN ELLGRQILDG
APDQLRWRNV LKRNELDWLD GHQVQRQTVF PFMGYVSACV EAAMKIRGDA NVQSIELQNF
KVGQAVAFND DDSWIEILVV LDSIKESKVK GTKTISAHFA FHSSSNNETV DMTTHAGCDV
LVTYGDSISD LLPPPEIQAD DEYFMLGVES DRFYNVLDDI GLGYTGPFRA LSGLQRKLGK
ATGRIKNPAS SKLWRKPLLV HPAMLDAGIQ SIMLAYCYPG DTMMRSIYLP TGIRRLIINP
EHCQTFAGEE TDVLFQSSAS VDDPQGLSGD VSIYAPGGLS CKAIQVEGLQ TQPLFNPTEA
NDLNIFTELV WGVDRPDAKE IVNKVDVQQL DGDLLFSLER VAYYYLRILD KSIPLSQRTG
IDWHFGQLFA YVDHVLSRVE RGTNRFARKE WQHDTKEIIL EILERYPDNI DLRLMRAVGE
NIAAVIRGEI TMLEPMLQNN MLNDFYVVAH GMPRYTKYLA SLASQIGHRY PHMHVLEIGA
GTGGATKSFL GALDDKFSTY TFTDISSGFF EKARSVFASY SAKMSFKMLN IEKDIGDQGF
VEGSYDVVIA SLVLHATRNL GQTLRNVRRL LKPGGYLLLL EITENDQMRF GLLFGGLEGW
WLGYDDGRAL SPCINIEEWE KYLKQTGFSG IDTLMPHDEI LPVPLSVIVS QAVDERTELL
KQPLQRLDPS TTLVPQLTII GSGALAEEVH RLLRPFCGRV NVIESLGHMG ADQLPVGGAV
ICLADIQEPV FKSMDADKLR GFQTIFKQSG SALWVTQGTL NGNPYSRMVI GFGRTIVLEM
LHLRLQFLDL DHEAPADPTA IVETFIRLHL AENWKNDGVK ITPLLHSVEP EMHIDKEGRG
FIPRFKLNKK QNDRYNSGRR KIVKEVPLRQ QPVELVPPKS EDASWLLAEG KNMPELKGAI
DIDVFYTVTR AVEVSGGTFL YAVLGARRDT KEVVLALSPT QASIIRVPQA FIIPAQDSVE
YLQLFYTELL ARAVLRDVAA GTVVVVLRPT SMLSCAVDRL AADRGARVLH LADEPGSDWD
YLHHKSSKVQ VQDWVKSRLG TEAPPAVLLL DFGADQFLLA YLLECLPAEV TRAMVGAQST
SSKARMKLGQ SEQEIRSFLA DVRYALLPAQ QTHQSSKGRS SLKVFTLEHL TTNRAGSDVS
VVSWPAGTST IPVQVQPVNS KVTFSNDKTY WLVGLSGTLG LSLCEWMAQQ GARYIVITSR
NPNVDERWKN KMEKLGIKVE IIANNICDRK SVRSVYSHIC QTMPPIGGVA QGAMVLHDTA
FSELDLERIN KVMQPKVNGS IYLEEIFHNT PLEFFVFFSS MACVTGNPGQ SAYAAANMFM
SGLAVQRRKR GLNASVVHIG AIFGNGYVTR ELSLEQQNFL RKVGNMWLSE QDFRQLFAEA
VLAGQPENTG SPELSTGMMT IDNSEGTKEN ITWFDNPMFQ HCIKESTDGK LGGQTAKGRA
VPVKTQLLEA INSAEVYEII HDAFAAKLRS SLQLEDDRPI VDQTADTLGI DSLFAVDIRS
WFIKELQLEI PVLKILGGAT VGEILETAQQ LLPMELLPKM DPNDKSPARK LKAQPDSSPD
KAASAERSRA KAQTAIENDG DRKFAATRAE SGAKKGETVS KKVEAVTRPS VQWQVPVEPS
TAVGDLDDKS FPGEDGVRLR AGSLDTTFTH KSSASSSASI LDASEDQSAD SVWSLDTVNN
ELAVSKKTPI SFAQSRIWFL EKFLEDPASA LNITLTIELD GSLDVDRFGK AVKLVGQRHE
ALRTRFVHGD DFDAPMQEVL VHSTLSLEQQ DIASDAEADE VYRELQKYRY KLGEGENMRI
ILLKKSNQLF HLVIGYHHIN MDGVSLEVVL RELQMAYDSK RLPNFGTILQ YPDFAALQQK
EYKSGAWQDE IEFWRKEFDG RPPSVLPLLP MAKTRSRTAL TSYSSHTAEF SLDQITLAGI
QSACESSKAT PFQFHLATFY ALLSRMVDAA DICIGIGSAN RHDTAMMQSV GIYLNLLPIV
LKSQPNETFA STLKRVRSKV MTAFAHSRVP FDVIVNELGA SRATTHNPLF QVLVNYRQGT
ATRRSFCGCQ SEVRSFEQGQ AAYDLGLDII ENPGGECKVI MTGQSTLFVP EDMDMLKDMY
QRLLLAFSRN QALRLAIPSL YDPEMVKHAL RIGRGPSYTH KWPETLIHQI DDIAKQKSHS
LAIVDGSGTF LTYAHMSRRT NAIAASLRGI RRGSRVGVHL DPGADWVCSV LAIMRRDAVY
LPLDAVSGYS RLSAILQDSK PDLVLVDNST EKDATAYFSP ILAADQIFNI DTVSVTPPET
LAIAAKRGSV AALMYTSGST GVPKGIIMKH ESFRNNIEII SEKLGYNNGH TVTLQQSSFN
FDMSLGQIFL ALSTGGTLHV VPRHLRADPV AISSIIALHG ITNTSATPSE FISWVRYGSV
EELRNSAWAA VHSGGEPVRD SLKAAFLTVN KPGLRLLDCY GPTEVTFCSH ISDVDYGAEE
TSMNKGLEVL PNYATYIVDS GMKPVPAGVP GEVLIGGAGV VAGYLHTELN TRGFAHDSFA
SDEFRKQGWE QLHRTGDFGR INKLNGRLLL EGRIADDTQV KLRGLRIDLK EIEAAMVRAA
KGDILDCIVS VAQSADVSDE YLVAYATARP DASNHRLEHL MHQLPLPQYM KPATLVLLEK
MPTNASGKID RSAFKSIPLP KATEDNGMQP EVGQDLNDTE SRLKQLWEGV LPKHVFSQHK
FTAASDFFNV GGSSMLLISL RAKIQDTFAV VVSLFQLFEA STLGDMAALV DELSSGSAEK
TAGPNSALDI NWEDETAVSP ALLGIPVEKK FFTNPEIVVL TGSTGFLGRA ILTRLLNDGI
VKEIHCFAVR EEIPLFDSPK IIVHRGDLTL PGFGLSQKEL ASIFSKAHAV IHNGADVSFV
KSYHSLKPAN LEATKQLVDL CLPYQISFHY ISTAAVVNLT GEKSWEQRSV GRFPPPAGTD
GYIATKWASE RYLEKFNDQY GLPIWIHRPS SITGPGAPAN DLMANVVEFS RSTAATLNTN
SWSGWLDFIS VDEAALQIVD EVYEDYSWPG HVKYLYESGE RVVALEDMKN VLEREVGSVF
EVVDVEEWIS RAEKQGFNPL LGEYLKRVAN APLVFPKLIR HEGFF
