ID   APMA_PENBR              Reviewed;        2346 AA.
AC   A0A1W6BT53;
DT   11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT   05-JUL-2017, sequence version 1.
DT   03-AUG-2022, entry version 21.
DE   RecName: Full=N-benzoylphenylalaninol synthetase apmA {ECO:0000303|PubMed:29719714};
DE            EC=1.-.-.- {ECO:0000269|PubMed:29719714};
DE            EC=6.3.2.- {ECO:0000269|PubMed:29719714};
DE   AltName: Full=Asperphenamate biosynthesis cluster protein A {ECO:0000303|PubMed:29719714};
DE   AltName: Full=Nonribosomal peptide synthase apmA {ECO:0000303|PubMed:29719714};
GN   Name=apmA {ECO:0000303|PubMed:29719714};
OS   Penicillium brevicompactum.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX   NCBI_TaxID=5074;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], IDENTIFICATION, DISRUPTION PHENOTYPE,
RP   FUNCTION, CATALYTIC ACTIVITY, DOMAIN, AND PATHWAY.
RX   PubMed=29719714; DOI=10.1039/c7sc02396k;
RA   Li W., Fan A., Wang L., Zhang P., Liu Z., An Z., Yin W.B.;
RT   "Asperphenamate biosynthesis reveals a novel two-module NRPS system to
RT   synthesize amino acid esters in fungi.";
RL   Chem. Sci. 9:2589-2594(2018).
CC   -!- FUNCTION: Nonribosomal peptide synthase; part of the gene cluster that
CC       mediates the biosynthesis of asperphenamate, a rare linear amino acid
CC       ester that exhibits antitumor activity towards a number of cell lines
CC       (PubMed:29719714). The structure of asperphenamate contains two
CC       subunits, N-benzoylphenylalanine and N-benzoylphenylalaninol, which are
CC       connected by an inter-molecular ester bond (PubMed:29719714). The first
CC       step of asperphenamate biosynthesis is the generation of N-
CC       benzoylphenylalaninol by the nonribosomal peptide synthase apmA
CC       (PubMed:29719714). Using phenylalanine and benzoic acid as substrates,
CC       apmA catalyzes amide bond formation and tethers the intermediate into
CC       the NRPS chain. Then, the terminal R domain of apmA catalyzes the
CC       reduction reaction to get the shunt product N-benzoylphenylalaninol
CC       (PubMed:29719714). Subsequently, the nonribosomal peptide synthase apmB
CC       activates the same substrates as does apmA (phenylalanine and benzoic
CC       acid) to produce N-benzoylphenylalanine before condensing N-
CC       benzoylphenylalanine and N-benzoylphenylalaninol to release
CC       asperphenamate (PubMed:29719714). {ECO:0000269|PubMed:29719714}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=2 AH2 + 2 ATP + benzoate + L-phenylalanine = 2 A + 2 AMP + 2
CC         diphosphate + H(+) + N-benzoyl-L-phenylalaninol;
CC         Xref=Rhea:RHEA:59476, ChEBI:CHEBI:13193, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:16150, ChEBI:CHEBI:17499, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:33019, ChEBI:CHEBI:58095, ChEBI:CHEBI:145107,
CC         ChEBI:CHEBI:456215; Evidence={ECO:0000269|PubMed:29719714};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:59477;
CC         Evidence={ECO:0000269|PubMed:29719714};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:29719714}.
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       methyltransferase domains (responsible for amino acid methylation) are
CC       present within the NRP synthetase. ApmA has the following architecture:
CC       A-T-C-A-T-R with a C-terminal reductase (R)-domain that acts in the
CC       reductive release of the shunt product N-benzoylphenylalaninol in the
CC       two-modular NRPS apmA. {ECO:0000305|PubMed:29719714}.
CC   -!- DISRUPTION PHENOTYPE: Completely abolishes the production of
CC       asperphenamate. {ECO:0000269|PubMed:29719714}.
CC   -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR   EMBL; KX443597; ARJ55264.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A1W6BT53; -.
DR   SMR; A0A1W6BT53; -.
DR   GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR   GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR   GO; GO:0009058; P:biosynthetic process; IEA:UniProt.
DR   Gene3D; 1.10.1200.10; -; 1.
DR   Gene3D; 3.30.300.30; -; 2.
DR   Gene3D; 3.30.559.10; -; 1.
DR   Gene3D; 3.40.50.12780; -; 1.
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; IPR013120; Far_NAD-bd.
DR   InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR   InterPro; IPR009081; PP-bd_ACP.
DR   Pfam; PF00501; AMP-binding; 2.
DR   Pfam; PF00668; Condensation; 1.
DR   Pfam; PF07993; NAD_binding_4; 1.
DR   Pfam; PF00550; PP-binding; 2.
DR   SUPFAM; SSF47336; SSF47336; 2.
DR   SUPFAM; SSF51735; SSF51735; 1.
DR   TIGRFAMs; TIGR01733; AA-adenyl-dom; 2.
DR   PROSITE; PS00455; AMP_BINDING; 2.
DR   PROSITE; PS50075; CARRIER; 1.
PE   1: Evidence at protein level;
KW   Ligase; Oxidoreductase; Phosphopantetheine; Phosphoprotein; Repeat.
FT   CHAIN           1..2346
FT                   /note="N-benzoylphenylalaninol synthetase apmA"
FT                   /id="PRO_0000448646"
FT   DOMAIN          784..860
FT                   /note="Carrier 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   DOMAIN          1842..1924
FT                   /note="Carrier 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   REGION          263..652
FT                   /note="Adenylation 1"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:29719714"
FT   REGION          896..1306
FT                   /note="Condensation"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:29719714"
FT   REGION          1330..1713
FT                   /note="Adenylation 2"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:29719714"
FT   REGION          1960..2311
FT                   /note="Reductase (R) domain"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:29719714"
FT   MOD_RES         821
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   MOD_RES         1883
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ   SEQUENCE   2346 AA;  255547 MW;  C28D56FECCC5A28A CRC64;
     MPSIVIDDAD RLRQLWTQLV TDVTPSHLPS GLFSKRETKS TVGRLNVPMQ LSAIYDCCQQ
     CDVSPLNVVQ AAWTAVLRSY SGADNVMFAG IGMNPRSTKQ QWTNTSVSLA RLEQDSSVIS
     VLDTTQEEGL LQAESMVSVP EALDIFSSLE PKPCNSAIWL KDAQSKSELS LTDVVNEKTF
     DYAVQIDASL TQLDLVFHKP TVSRSQAQYI ASTFADYLQS VCLDPYQTAS TVCHPSELDM
     MQIDTWNRIL PKGSEVCVDQ LIESAAQKSP DAQALVGWDG EMSYSQFNQA ANKMAAYFDS
     VGVQRGELVP ICFEKSVWTI VTMIGLWKLG AGWVPLDPKH PRQRLETIIE SVGARTVIAS
     ASNKDLVQDI ASQVLILDPS QIQSAPEVDF KSRSQPHDTS FVMFTSGSTG KPKGVVHDHA
     SVASSALNHA SAMNISNNTR ALQFGAYTFI ISTFEIFTTL IFGGCLCIPS DHDRHTDIRP
     AIRSFEANWA IFTPSFARSL HHEDIPSLDT LLVAGEAVAQ DIIDRWAPVA QLINIYGASE
     CSVVMIGRMV ADTPRSCIGR ATGGLSWLVD PNDHDRLVPI GSVGELVIEG PILARGYLAD
     PEKTQAVYIE NPVWASQSGN TRRFYKTGDL ARYGDDGRVH LIGRKDLQVK IRGQRVELTE
     IEAHMRAIDN SVKTAVAMVR PGGKAMLAAF ISNQSGFGPE FPHPFYSAPD DKQSVVSLAG
     QMSKKLTLQL PPYMIPSVFL PLAYMPLTAS GKTDRRLIAS FGDSLTLTEL AAVAGNGKVT
     ERRMPTTTTE MTLRQIWAEI LHCPVDEIGA EDNFFHLGGD SIEAMNLTRR CRAEGFQLQV
     GDILGNLVLS DMAKAMTSTR SLKPSITTPF ELLGDDTDAV RANILSATGL PAGLLQDAYP
     CSPLQMGLMA LSAKIPGSYV ARHTLELPSS VTVGRFKEVW GMIVESNDVL RTRIVETDEY
     GSVQVVNRAP LVWAHDTDLA KYIELDEKIP MQIGDALAHF GIIAGPTNTF VLTIHHSIYD
     GMSLEMIFND LVHAFEGVVP PVRTQFRDFI KEVVERNADK ATEEYWRGEF AEGDMTTFPS
     LPSASHQPLA NDSFVHTLQL NRKGPSDFTS ATLIRAAWSL VQARYCDSPE TVFGCTLSGR
     NAPVPGVEDV VGAVIATVPI KAKVDGEQPV AEWLQQINSH SVEMTPAQNY GLQNIARVAE
     GAAAACNFQS LLVIQPATSV AEDSIMQPFS APQANFSTVA LTLECSLAVD GSIQIHVHFD
     DTVLPRLEVQ RIVRQFEHVL QQLASAPAGK LSDIEIISPQ DKENLLQWNR DLAEPVNECV
     HRLISQNNFS QPNAPAICAW DGELTYTELE SLSSKLAAHL INVGVGPDVF VPLCFEKSMW
     TIVAMLATLK AGGAFVAMDA SQPISRMQSV VKDVNAQVVL YSEEQLSRAP GLAAKAIAVG
     PGMRELNTPR TPPTPVAPSN AAYVIFSSGS TGTPKGSVIE HRAFCTAAVS QKEGLQMGSR
     VLQFASYAFD ASILEILSTL VQGGCVCVPS ESERRGNIAE AITRMNVDWA VLTPSFVNTI
     DPSSVPTLST LALAGEAMSA AHVAAWTPYV RLVNGYGPSE CCVCTTSNRR VLPGTASNNI
     GTAVGSASWI TDRDDHNKLA PIGAIGELLI EGNILARHYL NNPEKTDAAF ITQPAWLPGH
     RSTRVYKTGD LVKYAPDGSI LFIGRKDTQV KIRGQRVELG EIEYHLNLPA DVSQSVVSYP
     KSGLYAQKLV GILELNSTAG SDLSVVPSAE FQRSGFQLSS LTHTLSETLP VHMIPVIWIV
     VRKIPSSSST KIDRKVVDQW LTKLPSNFEP TLGITREGPT TSALRASEDK ALAISKKIES
     LVNREDSPLH GRDFNISSMG IDSVQVISLA SFIKQSYGVK VDVSRVLDGQ MTVRGLAAFI
     DAELSGTVQE ALPAFDAMKE ASALVNDIIK NSMPQKTVFV TGGTGFLGTQ ILRQLCDRPD
     VGRVIAHVRA NSPSDAFIRI KDAAVRAQWW SDYYLTKLDV WCGNLASPKL GLKPKQWASL
     SGESPNDGLV NGIIHAGAAV NWNAGTEILR AANVNSTAEL IKAAISSPAR PRLSYVSGGS
     RWSVGENDQD IANEIAHANG YAQTKYLSEL LVKQFAAKYP NQFAIVKPGL ILGTPEEGVA
     NTDDFVWRLA SGVVDACAFS DDYANAWMYV TSSTRVAEET IAQVFCPAGS MKTVTYMTEG
     ITEREFWEIF HGELKYPLRK VDHETWMETM RKSIQKDTSS HPLWPVSQVF DALQGRLGGE
     PLQDASFVSP SQKQHVKATI RRNVQFLVEA GFIASPTGKK MKYMADKVFK RSGNVWENVK
     RMTITA