ID   CHYA_PENRW              Reviewed;        2382 AA.
AC   B6HLP9;
DT   28-FEB-2018, integrated into UniProtKB/Swiss-Prot.
DT   16-DEC-2008, sequence version 1.
DT   03-AUG-2022, entry version 80.
DE   RecName: Full=Nonribosomal peptide synthase chyA {ECO:0000303|PubMed:29196288};
DE            Short=NRPS chyA {ECO:0000303|PubMed:29196288};
DE            EC=2.3.2.- {ECO:0000269|PubMed:29196288};
DE   AltName: Full=Chrysogine biosynthesis cluster protein A {ECO:0000303|PubMed:29196288};
GN   Name=chyA {ECO:0000303|PubMed:29196288}; ORFNames=Pc21g12630;
OS   Penicillium rubens (strain ATCC 28089 / DSM 1075 / NRRL 1951 / Wisconsin
OS   54-1255) (Penicillium chrysogenum).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium;
OC   Penicillium chrysogenum species complex.
OX   NCBI_TaxID=500485;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 28089 / DSM 1075 / NRRL 1951 / Wisconsin 54-1255;
RX   PubMed=18820685; DOI=10.1038/nbt.1498;
RA   van den Berg M.A., Albang R., Albermann K., Badger J.H., Daran J.-M.,
RA   Driessen A.J.M., Garcia-Estrada C., Fedorova N.D., Harris D.M.,
RA   Heijne W.H.M., Joardar V.S., Kiel J.A.K.W., Kovalchuk A., Martin J.F.,
RA   Nierman W.C., Nijland J.G., Pronk J.T., Roubos J.A., van der Klei I.J.,
RA   van Peij N.N.M.E., Veenhuis M., von Doehren H., Wagner C., Wortman J.R.,
RA   Bovenberg R.A.L.;
RT   "Genome sequencing and analysis of the filamentous fungus Penicillium
RT   chrysogenum.";
RL   Nat. Biotechnol. 26:1161-1168(2008).
RN   [2]
RP   FUNCTION, DOMAIN, AND DISRUPTION PHENOTYPE.
RX   PubMed=29196288; DOI=10.1128/aem.02246-17;
RA   Viggiano A., Salo O., Ali H., Szymanski W., Lankhorst P.P., Nygaard Y.,
RA   Bovenberg R.A.L., Driessen A.J.M.;
RT   "Elucidation of the biosynthetic pathway for the production of the pigment
RT   chrysogine by Penicillium chrysogenum.";
RL   Appl. Environ. Microbiol. 0:0-0(2017).
CC   -!- FUNCTION: Nonribosomal peptide synthase; part of the gene cluster that
CC       mediates the biosynthesis of the yellow pigment chrysogine
CC       (PubMed:29196288). the NRPS chyA mediates the condensation of
CC       anthranilic acid and alanine into the intermediate 2-(2-
CC       aminopropanamido)benzoic acid (PubMed:29196288). The remainder of the
CC       pathway is highly branched yielding at least 13 chrysogine-related
CC       compounds (PubMed:29196288). The malonyl transferase chyE converts 2-
CC       (2-aminopropanamido)benzoic acid and 2-(2-aminopropanamido)benzamidine
CC       into 2-(2-(2-carboxyacetamido)propanamido)benzoic acid and 3-((1-((2-
CC       carbamoylphenyl)amino)-1-oxopropan-2-yl)amino)-3-oxopropanoic acid,
CC       respectively (PubMed:29196288). ChyD is an amidase, being responsible
CC       for the amidation of the carboxylic acid moiety of 2-(2-
CC       aminopropanamido)benzoic acid, 2-(2-(2-
CC       carboxyacetamido)propanamido)benzoic acid and 2-(2-((4-amino-1-carboxy-
CC       4-oxobutyl)amino)propanamido)benzoic acid (PubMed:29196288). ChyC is
CC       involved in the same reactions as ChyD, but plays a more minor role in
CC       the amidation reactions compared to chyD (PubMed:29196288). The
CC       oxidoreductases chyH and chyM are involved in oxidation reactions that
CC       form N-pyruvoylanthranilamide from 2-(2-aminopropanamido)benzamidine
CC       and (1-((2-carbamoylphenyl)amino)-1-oxopropan-2-yl)glutamine,
CC       respectively (PubMed:29196288). N-pyruvoylanthranilamide is further
CC       converted via two further branches in the pathway, yielding chrysogine
CC       and additional chrysogine-related coumpounds (PubMed:29196288).
CC       Chrysogine is likely formed by a spontaneous ring closure from N-
CC       pyruvoylanthranilamide (PubMed:29196288).
CC       {ECO:0000269|PubMed:29196288}.
CC   -!- PATHWAY: Pigment biosynthesis. {ECO:0000269|PubMed:29196288}.
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. ChyA has the following
CC       architecture: A-T-C-A-T-C. {ECO:0000305|PubMed:29196288}.
CC   -!- DISRUPTION PHENOTYPE: Impairs the production of chrysogine and 13 other
CC       chrysogine-related compounds (PubMed:29196288).
CC       {ECO:0000269|PubMed:29196288}.
CC   -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR   EMBL; AM920436; CAP96160.1; -; Genomic_DNA.
DR   RefSeq; XP_002568290.1; XM_002568244.1.
DR   AlphaFoldDB; B6HLP9; -.
DR   SMR; B6HLP9; -.
DR   STRING; 1108849.XP_002568290.1; -.
DR   EnsemblFungi; CAP96160; CAP96160; PCH_Pc21g12630.
DR   GeneID; 8306449; -.
DR   KEGG; pcs:Pc21g12630; -.
DR   VEuPathDB; FungiDB:PCH_Pc21g12630; -.
DR   eggNOG; KOG1176; Eukaryota.
DR   eggNOG; KOG1178; Eukaryota.
DR   HOGENOM; CLU_000022_60_2_1; -.
DR   OMA; AEACNFQ; -.
DR   OrthoDB; 4243at2759; -.
DR   BioCyc; PCHR:PC21G12630-MON; -.
DR   Proteomes; UP000000724; Contig Pc00c21.
DR   GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016740; F:transferase activity; IEA:UniProtKB-KW.
DR   Gene3D; 1.10.1200.10; -; 2.
DR   Gene3D; 3.30.300.30; -; 2.
DR   Gene3D; 3.30.559.10; -; 2.
DR   Gene3D; 3.40.50.12780; -; 2.
DR   InterPro; IPR010071; AA_adenyl_domain.
DR   InterPro; IPR036736; ACP-like_sf.
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; IPR009081; PP-bd_ACP.
DR   InterPro; IPR006162; Ppantetheine_attach_site.
DR   Pfam; PF00501; AMP-binding; 2.
DR   Pfam; PF00668; Condensation; 2.
DR   Pfam; PF00550; PP-binding; 2.
DR   SUPFAM; SSF47336; SSF47336; 2.
DR   TIGRFAMs; TIGR01733; AA-adenyl-dom; 1.
DR   PROSITE; PS00455; AMP_BINDING; 2.
DR   PROSITE; PS50075; CARRIER; 2.
DR   PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE   3: Inferred from homology;
KW   Ligase; Phosphopantetheine; Phosphoprotein; Reference proteome; Repeat;
KW   Transferase.
FT   CHAIN           1..2382
FT                   /note="Nonribosomal peptide synthase chyA"
FT                   /id="PRO_0000443345"
FT   DOMAIN          745..821
FT                   /note="Carrier 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   DOMAIN          1833..1909
FT                   /note="Carrier 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   REGION          204..607
FT                   /note="Adenylation 1"
FT                   /evidence="ECO:0000255"
FT   REGION          857..1269
FT                   /note="Condensation 1"
FT                   /evidence="ECO:0000255"
FT   REGION          1294..1687
FT                   /note="Adenylation 2"
FT                   /evidence="ECO:0000255"
FT   REGION          1967..2373
FT                   /note="Condensation 2"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         782
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   MOD_RES         1870
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ   SEQUENCE   2382 AA;  260769 MW;  582DAC279F7F88E7 CRC64;
     MAAPSISPLF APQMGVQRDF QDSEMQIATV NFPCTGQSNT SLANWLQQEE KSHLQLLQAA
     WSISLRSYTG SNDVLFSCLN TKDTAALGAN SVVYVDEGNE DKYGSARRGN LREFDLAICF
     SKQNEANCPV IGIHHKPSVI STDFATMIAA TVAKAIEEIV LHVDSLIASL DICSDADINC
     ISRWNSPSDD GIPSAQCIHH IISQKCATQP ESIAVSAWDG RLTYAELDGL SSSLAIRLQH
     LGVCQEIFVP LIFDKSKWAV IALLSVLKAG GAYFFLNPSN PIQYNLGLCS SLSPEVALCS
     PRHSTLAKSF AGTAIPVGEE HCELPESLPV DEKTPPCTAE TTPSNAMYIT FTSGTTGVPK
     GITTEHSAFY SMAMANGKAL QVGPATRMLQ FASYTFDVSN RDMLITLMFG GCICIPSELD
     RLNDLSGFIN RQSVNLASLT PSLASTLNPA LCPSLQGLVL GGESMNDSHI SAWANHVRLF
     NAYGVSESAG IAALASDIQA DYSPGNIGFG SGSTLWVVTI DQPDKLAPIG ALGEMVIEGP
     SVARGYLGDK KRTEEQFTST SKWKNRIRAQ LSESRSSKRA FHTGDLVRYN LDGSLNFLGR
     KDHQVKIHGQ RLELTAIEHH IAACLEVAES GFLHVAVVTA KNEGNGSVKL LAFLGLYTSR
     GSDSPSQLVS KKLEDVEALK VALRQHLLLC LPAFMVPVDF IFVQHMPLTT SGKINRLLLQ
     EAAGHALLDD QKRNIDTSDL NGNQTPTTQN QRILIQSWAK ALGIKSESIM RNDCFFRRGG
     DSIAAIKMAA SLRQQELIIS VSDVFKFSTF SDMASVLVKD HRPLQTAMLA PFSLIDNSQT
     VLDAVMEELG TGIDQIEDVY PCTHMQQGLI ALTAQQPHSY IGRYTWQLAE MLDVEKFKNA
     WESAWLHNPI LRTRIVQIPD GVFQVVVKTD MPWNTVTDIS RGGDGKELRE IDISNGPLIQ
     FYLSKESFRL DIHHSLFDEW SLGLIMGQVE RAYAGGGLRM QPFSPFVQHL LHERDTSLED
     FWRQEFSGLQ AEHFPAIASR PLSVEHPTEK VVLEHSVQLE TGFSTKYTIS SIVRLAWAIV
     LWHQTGSEDV VFGATVSGRN ANIDGIDQLS GPTLATLPVR IKLAASQPIH EGLSQVQGQF
     VNMMVHEQAG LPRIRQVGRE AAEACNFQNL LVVQPYEEQT ESHMFKASAN SASSSENAKS
     FASYPMVLIC RPEKSGISMK AAFDPAILTP AAGHSILKQM SHVIQQLVTS DSTCIAAVSL
     VPPEDMATLR QWNHSLPNGV NTCIHARIQE LCIGQPDTLA IHSQNLDLTY GQLDNYSDQF
     AQNLIGSGVK QGDFVPLFLE RSPWVPVIML AVLKTGAAFV LLDLSHPMQR LRTMCSMIDA
     RIVVTSKEHA DRSGNLLLPV IIFDPEAHAQ NVSKQATAPE LKPLTAVTTP DAPACVVFSS
     GSTGLPKGIV LPHSALTTSA AVMREYGMLG PKSRVFHFAS FAFDISIGEI LFTLAAGACV
     CVPHEEERKG NPAKAAGDLK VTWALLTPSV INLFDPSDVP TLEVLGSAGE PLTPQIVDTW
     AHRVKLYGMY APAECTVISH IGRILPDTHH SNIGKSHGGV SWVVDPSDHN RLVPIGTVGE
     LIVEGPTVSS GYLNDPAKTN EVFITSPSWL DEVRSHSGKM YKTGDLVRQT SEGSLEFVGR
     KDDQVKLHGQ RLEVGEVEHC ITSSCTAIKT ATVECIKIRE QNSRVSLVAF ICPQTDEDWG
     QSLNDPSSEV GDLELISPPR DQFYSMIESL ETSLRELLPA YMVPSFFVPL ADVPLSLSGK
     VNRRLLRDQS TSWPMKRLGL YQLRRKSIPA EEVPVSIHGR KVQEIVGQAL NLDPKSIPMN
     SNFFGLGGDS ISAMQVSMLA RRRGIRLTVA DIFTQQTLSG LSLKCATENG DASQASKSRS
     LGRELPGSNI KSLHRCEIPR DKLPRQLPQE IADNIVEAMP ATEFQTMTLH NFYSRYLWIS
     LPERVNQEHL LNACDQLVQK HSVLRTVFYT NDDKSVVQLT LRKVPVNFVH YSNIENLEKH
     CADDSLAMGV PINSVPGFEV QLVTLRDSGM YLILRLPHAQ FDGVSLDIIC SDLSAAYSGD
     SLPPCAQFSD HIRHVWEKRI PESYNAWREV LGNVPMTSLN NKYLRNWGSA SEMGSPNMGT
     DPDQPKVVTA MAETLPISPP PNITLATLVK LAWAITLSRL FTSIEEDDGA SDDVVFGQVV
     HGRGLGISHE DRIVGPCLNI IPVRVHLPPR SNKLDLLGQV QQQHIQTMSV ENLELGEITR
     NCTSWKAGTK FGSFIRFQNF TNNDDSTCSF DGSACETGLY SLPNRPSNTA NVLVVPHGPT
     LSITMTISNQ VLDRGSADFV AGYFSDVIES LASEETVCEY LE