ID   VALB_ASPTE              Reviewed;        2637 AA.
AC   P9WEV1;
DT   12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT   12-AUG-2020, sequence version 1.
DT   25-MAY-2022, entry version 7.
DE   RecName: Full=Nonribisomal peptide synthetase valB {ECO:0000303|PubMed:28604695};
DE            Short=NRPS valB {ECO:0000303|PubMed:28604695};
DE            EC=6.3.1.- {ECO:0000305|PubMed:28604695};
DE   AltName: Full=Valactamide biosynthesis cluster protein B {ECO:0000303|PubMed:28604695};
GN   Name=valB {ECO:0000303|PubMed:28604695};
OS   Aspergillus terreus.
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Circumdati.
OX   NCBI_TaxID=33178;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DOMAIN, DISRUPTION PHENOTYPE,
RP   AND PATHWAY.
RC   STRAIN=ATCC 20542 / MF4845;
RX   PubMed=28604695; DOI=10.1038/nchembio.2408;
RA   Clevenger K.D., Bok J.W., Ye R., Miley G.P., Verdan M.H., Velk T., Chen C.,
RA   Yang K., Robey M.T., Gao P., Lamprecht M., Thomas P.M., Islam M.N.,
RA   Palmer J.M., Wu C.C., Keller N.P., Kelleher N.L.;
RT   "A scalable platform to identify fungal secondary metabolites and their
RT   gene clusters.";
RL   Nat. Chem. Biol. 13:895-901(2017).
CC   -!- FUNCTION: Nonribisomal peptide synthetase; part of the gene cluster
CC       that mediates the biosynthesis of valactamides (PubMed:28604695). The
CC       first step of the pathway is performed by the highly reducing
CC       polyketide synthase valA that produces the polyketide part of the final
CC       products (Probable). An acetyl starter unit is incorporated by the
CC       ketosynthase domain of valA, and subsequently 6 malonyl-CoA-derived
CC       ketide units are incorporated and fully reduced to their respective
CC       alkane forms by the action of the ketoreductase, dehydratase, and
CC       enoylreductase domains (except for the penultimate unit, which is
CC       reduced only to the alkene) (Probable). The final five ketide units are
CC       each proposed to be alpha-methylated by the methyltransferase domain
CC       before ketone reduction by the ketoreductase domain (Probable). The C1
CC       domain of the nonribisomal peptide synthetase valB then catalyzes amide
CC       bond formation between the heptaketide chain and L-valine (L-Val)
CC       attached to the T1 domain (Probable). The C2 domain incorporating L-
CC       isoleucine (L-Ile) then carries out chain elongation, which is followed
CC       by macrolactonization by the Ct domain to release the final product
CC       (Probable). {ECO:0000269|PubMed:28604695, ECO:0000305|PubMed:28604695}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:28604695}.
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. BenZ as the following bimodular
CC       architecture: C1-A1-T1-C2-A2-T2-Ct. {ECO:0000305|PubMed:28604695}.
CC   -!- DISRUPTION PHENOTYPE: Abolishes the production of valactamides A-H.
CC       {ECO:0000269|PubMed:28604695}.
CC   -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR   EMBL; KX449366; AQM58286.1; -; Genomic_DNA.
DR   AlphaFoldDB; P9WEV1; -.
DR   SMR; P9WEV1; -.
DR   VEuPathDB; FungiDB:ATEG_03576; -.
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; -; 3.
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; 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; 3.
DR   Pfam; PF00550; PP-binding; 2.
DR   SMART; SM00823; PKS_PP; 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; Repeat.
FT   CHAIN           1..2637
FT                   /note="Nonribisomal peptide synthetase valB"
FT                   /id="PRO_0000450620"
FT   DOMAIN          946..1022
FT                   /note="Carrier 1"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT                   ECO:0000305|PubMed:28604695"
FT   DOMAIN          2078..2154
FT                   /note="Carrier 2"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT                   ECO:0000305|PubMed:28604695"
FT   REGION          1..376
FT                   /note="Condensation 1"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:28604695"
FT   REGION          413..803
FT                   /note="Adenylation 1"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:28604695"
FT   REGION          1016..1045
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          1063..1506
FT                   /note="Condensation 2"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:28604695"
FT   REGION          1524..1933
FT                   /note="Adenylation 2"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:28604695"
FT   REGION          2193..2582
FT                   /note="Condensation 3"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:28604695"
FT   MOD_RES         983
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   MOD_RES         2115
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ   SEQUENCE   2637 AA;  288817 MW;  CAA27F2EB7825D62 CRC64;
     MADGADYTQR NIHSLDSSLD LDRFCASLHQ VVASNQILRT RIVDCPLGLV QVIVKSEAFI
     DCLSRPCNAD VEQYLRQDEM SPMHLGMPLA RFAIVGRKLV TTIHHAIADS HSLLYLYEDA
     WKIYQGESPP PRAPFREFVD YCKSIDSKSA AAFWKSQFSE SAPGVFPTVP SGHLIKASQT
     AAHTISLAKK PPLPLLPAYI EAAWAMTAAD YTGSENVVFG YVMSGRTAIG GAETTLGPTI
     STVPMQVQLN ASASIEQLLK SRTQFRRSLL ASPFLQYGLA NIRHTVSDEA HVASGFQTLL
     DILSVDETQA NAPGLTLERT IHTYVHGLTL MCKIAGEDIL VRADFDSIVL PDAQVQRILR
     QMEHRLKALI RSPPSTELRN LSPLNLSDTI EILDWNSDVP DAVNQCVHDI FTSQASRRPD
     AAAVHAWDGQ ATYHELDVMS DNLAHELLLR KISPEVPIAF TLERSLSAVV AVLGIMKAGG
     ACLPIELSFP RARKDAIVRV VGARLIVTSS THEAVEGCES IILDLHRVAH RGVDIRRRIN
     RDPARAAYIL FTSGSTGEPK GVVLEHRSLA TSYTAICNRV GWSSGTRILQ FSSPAWDAFA
     LEVLGPLMVG GCICIPSNIS RESALGEYIN SARVDSVLQT PTALRNLTPD DMLPSLKSLL
     VGGEPIPENA YKTWGSKVRL YNIWAPCETS TISTIADLSP LSVYPTSIGT PVGSAVWIVD
     RDDPSKLLPI GAVGEMLVEG PGVARGYHNN PTQTAPSFIS PPPFIPMRPN ASSPKVYRTG
     DLARYNPDGS IAFVGRRDNQ IKLRGQRFEM EDVEQVLGRH GCTCAVAVVN FKLPRQERED
     LVAFVTLSAV PGYHPSPQST DDELPAVPLN EDIRNQLQTL HDFTRGQLPP YMVPTAWVVV
     RHLPKLTSTK IDRVKLRQWL HEVDLSSARV IMRQFGDGRR THGLTPPANP PERALQLAWS
     SVLGVEEGHI GRESSFLSLG GDSITAMQVA SRCHKQGFSI RSTALLRAGT LAEAASEIKE
     PTDASAPSPS PISRDLPLQK SNHDRGLQGH LHPTSLCVPR DNVEAIYPCT ALQEGLLLAR
     MKHNGDEREY NNRFAFRLTT RCGIKVDITR VSNAWKALCA AHPILRTIFV PGLSQNGAFQ
     QIVLKDSAPS ISIHRVQANC SDTTELFRHQ ERLPFAHTQP PHRLSLYEGV GKAVYAILEI
     SHAIFDARTL RIILANIATG YTSCRAIKKG RSFSDYVARE QEREEVGRQY WKTYLAGAQP
     CILPRDSAME ETSSSIRGLE VPCQNAPGLL AFCRSQGVTI ANFIQAAWGV VLQLYTGLSS
     VYFGCSRSDQ DRLDGGEDIL GPLITMMVCK FSFEDRSVSG VHLLQIARED AARGMEQPGC
     SLSRLHDDLA LSNSPLFDTI MTVAHAWPTD LAPGEGDLVI EHTDSEGTTE YSIIVTVGYS
     KDSLNIHLAY QRARLSDSLV ECIARTFAQV ITRIIASPEE SVLQALQPER PESCLTLSRA
     DMSLLQRWNT PAPLAFKECF PQRAREVAHQ RPLAPAVCSW DQNLDYCQLD LLSDYLAHKI
     IAQYGIGAEA VVPFACEKAA SAIVILLAIS KTGAAFLPLD ITHPPERLAT VVADSGASLI
     IVNTPELRNK MAAWTRQSIF LARLDDIVEE TSVEQTLKIR SDLKSVTIEP SNAAYVVYTS
     GSTGKPKGVL VEHGNLAVGA EEHARRIGIT ARSRVLQLAS FAFDLAIGDV VYALCSGACL
     CVPSESDRNG NIAGVINRLH ANFLFTTPTQ LSVLTPEEVP TLRTVSVGGE PVGRQIIETW
     TPHVRLVIPY GPVETTIIVS CRDVTSGDQD GRDIGHPSSC RFWVVDPDNR DSLVPIGTPG
     ELVIEGPVVA RGYLHTSDAT GSAFIDPPAW SNAQEFASLN LASRRFYKTG DLVTQVGEKS
     FLIEGRKDTR VKLHGQRVEL GEIEYHLSHR VEPGWHWAVD IIQPRGGKDP CLAAFFVTDK
     SNIMETPTPA SGHELLEPLA EHASAAKETL KHVLPAYMVP EYFIRIRALP MLSSLKTDRK
     ALRTMAAGLS RAELLAYRVR ESVSNIGHAH SNPAKTQKEV TDDQAFMQQA WADVLGISSD
     EIGCGDNFFD IGGNSIRAIH LIARLRKSGH KLSVEEVFRA RTLAYMVSKT SVSNAQSGDQ
     PTSTPPAALD TESIPHLMHL AEKFPWLQRD NIESVAPATD AQAWMLDVSE RAGRGFDNGL
     TLIPLPGHAL SRPKLQRACQ EVLRQHPILR TVFVCCESQV LQVALRKPPI EQVHTDKGPP
     KLSSSSILNR LPTFYLTSDS GSTSCRSLEL RIHHALYDAI SLGHLLDDLG AAYKGRDLVT
     RPTQYHEWIS HIKAKETTDT YIFWRELLRG SMPRSLVSRR SNWSAPGNPT DSKICFKTRV
     DAIPVSYGTD ATVFNAAWSL VLSQVLEKQD VVFGYISANR SCALPGVDQI VGPCINILPV
     HARCNGDITA ASLVAELQRQ STDSIPHQHV GLLSILKNST DWPKGTLNSL VAFQNHEAID
     DIVKLGDVDC ALSANGRVGN SAEVCLGIEP QPDGQVGITL QYSSVSMPHE KVLWMGAYLD
     AALHAFPTHW TKTIDQLRHH IDANCNFPRP PENGELKGGA IPHNNAGTGR FIIEAAS