APMB_PENBR
ID APMB_PENBR Reviewed; 2327 AA.
AC A0A1W6BT46;
DT 11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2017, sequence version 1.
DT 25-MAY-2022, entry version 20.
DE RecName: Full=Nonribosomal peptide synthase apmB {ECO:0000303|PubMed:29719714};
DE EC=6.3.2.- {ECO:0000269|PubMed:29719714};
DE AltName: Full=Asperphenamate biosynthesis cluster protein B {ECO:0000303|PubMed:29719714};
GN Name=apmB {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 ATP + benzoate + L-phenylalanine + N-benzoyl-L-
CC phenylalaninol = 2 AMP + asperphenamate + 2 diphosphate + H(+);
CC Xref=Rhea:RHEA:61908, ChEBI:CHEBI:15378, ChEBI:CHEBI:16150,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:58095,
CC ChEBI:CHEBI:145105, ChEBI:CHEBI:145107, ChEBI:CHEBI:456215;
CC Evidence={ECO:0000269|PubMed:29719714};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:61909;
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. ApmB has the following architecture:
CC A-T-C-A-T-C. {ECO:0000305|PubMed:29719714}.
CC -!- DISRUPTION PHENOTYPE: Completely abolishes the production of
CC asperphenamate and leads to the accumulation of N-
CC benzoylphenylalaninol. {ECO:0000269|PubMed:29719714}.
CC -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR EMBL; KX443596; ARJ55263.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A1W6BT46; -.
DR SMR; A0A1W6BT46; -.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
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; -; 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; IPR020806; PKS_PP-bd.
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 SMART; SM00823; PKS_PP; 2.
DR SUPFAM; SSF47336; SSF47336; 2.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 2.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS50075; CARRIER; 2.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Ligase; Phosphopantetheine; Phosphoprotein; Repeat.
FT CHAIN 1..2327
FT /note="Nonribosomal peptide synthase apmB"
FT /id="PRO_0000448647"
FT DOMAIN 734..810
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 1816..1892
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 214..605
FT /note="Adenylation 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29719714"
FT REGION 845..1259
FT /note="Condensation 1"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29719714"
FT REGION 1281..1675
FT /note="Adenylation 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29719714"
FT REGION 1937..2260
FT /note="Condensation 2"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29719714"
FT REGION 2299..2327
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 771
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 1853
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2327 AA; 254063 MW; 7E5E412298F410F5 CRC64;
MLQVVPGSLD TAPCAFPTEN LPGRGFQSIP LDLSSSGAIA SEVLLRSWAV VLRYYVGSDM
IAFGRIDDTD PASQFAVCHG DIPATATLEE LKASSLSGNP NSLPLSEWIA SNTFNTIVWN
GTSFPLEKLE TTSCSLALLV SDTPSLAFAS HAIGENVAAA VAEGVAHVAD IITNQPQTTI
GAVDLFGAVS WSQLQEWNST VPNMIEVCMH DLIDTQAKSR PDSTALDCWD GSVSYAQLVD
YTSRLGSFLV TQNVGPEVFV PVCFDKSLWA VVSMIGVMKA GGAFVCIDPA QPVDRLETII
SEVNAQVALG APAYREALAG LVPNAIAIDA DFILSLPPST ELPRVLPKDA AFAIFTSGST
GKPKGIVHEH RTMCSSARRH AAALNINSTT RTFQFAAYTF IVNTFELFTP LVEGGCVCVP
SKEDRLGRTT GAMRDLNANW ACLTPSFLRS IKPEDVPQLK TLLLAGEPVQ QDNLDTWRHR
VKMLNMYGAS EASICVAGDL SGPVGRSTIG VGAGCTTWVV DPIDHDRLAP LGAIGELVIE
GPILAREYIH QPEKTAEVFI SNTPWMEEIR GALPSRAYKT GDLVRYGTDG RINLVGRKDM
QIKLRGQRVE LEEVEFHLRQ LIPRGTEVAV GLVKPVDQPD RPMLAIFASL TKAFGENFSP
VNEDLAADIE SRMAGWKDKL GDSVPGYMVP STVVKLNHMP LTASGKTNRK AIGDFACTLT
IAALTGAAKK EHKEPATATG KVLRGIWADV LSLKEESISS DDSFLQLGGN SIDAMKLVNL
TRDVQLGLSV AKIFTYPVLD EMADACTKVI VQSFEDVPFG LITGKTDSLI QEAALQCQVG
PLAIEDLYPC TAMQEGLMAL SDSREGAYVA QHSLSLGPSI DLNRFKKACQ KVVDAHPILR
TCIVYPEQSR ALQAVVQGEI EWHTAEDLET YAKEDKARPM CAGQLLTRYG LVPDGEGWTF
VWTVHHAVYD AWTLELTFDR LDKAYKGHPL ERDTTFKEFI QHMVTTDESE SDNFWREYLA
GATRNEFPSA VSTSKQPVAD SSVKYSMSLI RTDGLSGITV ASMIRAAWGI LIGSHSESDD
VVFGGIVSGR NAPIANADKL FGPGIAAVPV RVKFPDNDTL TIREFIGDVQ DQSTKMISFE
QAGLQNIRRV SSDATAACDF QTLLVVQPHK EKHLSTEEID LRAASEADAN FGTYALTLEC
SLKSDGVVCS AHYDSSLVSK ESVERILGQL ENLLHQMCSS SADKKLNELI FISSKDQESI
RGWNRHIPKP IHKTIHQMIA ERIAERPDHE AVCSWDGSLT YAELDQHASR LARRLAQLDV
QPESFVPCCF EKSTWAIPAM LGVLRAGGAF LNLDPSQPAN RIQLMIRKLK SKTIVCSPSQ
YDLCRSMGEE YNIVVFDTQS PEESLPDMPP VDVKPENAAY VIFTSGSTGE PKGTIIQHGH
YAIGSVTHAP AMLIDGNTRA LQFASFTFDA SLVETITILI TGGCICVASE EQRKRDVAEA
VRATRANWAA LTPSFVNLLS PDDVPSIKVL ILAGEAMSQS HIDTWGKRLR LVNGYGPSEC
CVASTSTIDV VPGVSPRNIG FTCSGASWVV MPTNHHRLMP VGSVGELVLE GWNVGRGYLD
EPAKTEAAFV ENPLWMDLGD EMRAPVVYKT GDLVRYNADG SLDFQRRKDT QVKLRGQRVE
LGEIEYRITQ SLPNKPHAVV DIVCPKDAPD QPRLVAFIQV PASEARRKPT SIFMLNQPES
MIPEPNERHV SSLSGLEDRL SDFLPMHMIP SAYIPVYHIP KMPSGKADRK TLIRIGSGLT
HRRMAEYSGA TEDARPPTTD MQITMQELWG ETLKMPAAQI NLNDNFLRLG GDSITAMRLA
SAARAKGIPL STATIFQHPT LEAISAVAET LSHQQRPQSF EPFSTLKSIP KDQLIDDIII
PQLGVPAFQI QDALESTDFQ SLAINGGLNQ TRGWSNYLIF DFEGPIDLRR LQVACEQLVA
HHAVLRTVFL STGSELIQVI LRSVAPEYSI HIQDEEDPTE SLIREDLARP PHLGEAIVRF
MLVKDDATHH RLIMRISHAQ YDGSSMPHLM HDLRVAYRGE ELPKRAQFSD FVRTQLHTSD
GSKSFYKDML SGSQMTSVVS HTKSSVTNVL NTMLAEMVPL VAFKDHGITA ATVVKAAWAL
VLADMAATAD VVYGHMVSGR NLPLDGVESM MGPCLNIVPV RANMNSMHTI LDLLRHIQQQ
QTDTIPHESL GFQQIIDQCT DWTPATRFSS VFQYQDFGGE EAAPGQPVSF ESVLKCTPGF
VCPAPDACDM SLLATPVARV DLPRRPSPAG DTRDGPTAAS DSPSRAR
