ID   ACRB_ASPA1              Reviewed;        1552 AA.
AC   A0A1L9WR63;
DT   12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT   15-MAR-2017, sequence version 1.
DT   03-AUG-2022, entry version 25.
DE   RecName: Full=Nonribosomal peptide synthetase acrB {ECO:0000303|PubMed:32234543};
DE            EC=6.3.2.- {ECO:0000269|PubMed:32234543};
DE   AltName: Full=Acurin A biosynthesis cluster protein B {ECO:0000303|PubMed:32234543};
GN   Name=acrB {ECO:0000303|PubMed:32234543}; ORFNames=ASPACDRAFT_122295;
OS   Aspergillus aculeatus (strain ATCC 16872 / CBS 172.66 / WB 5094).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC   Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC   Aspergillus subgen. Circumdati.
OX   NCBI_TaxID=690307;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 16872 / CBS 172.66 / WB 5094;
RX   PubMed=28196534; DOI=10.1186/s13059-017-1151-0;
RA   de Vries R.P., Riley R., Wiebenga A., Aguilar-Osorio G., Amillis S.,
RA   Uchima C.A., Anderluh G., Asadollahi M., Askin M., Barry K., Battaglia E.,
RA   Bayram O., Benocci T., Braus-Stromeyer S.A., Caldana C., Canovas D.,
RA   Cerqueira G.C., Chen F., Chen W., Choi C., Clum A., Dos Santos R.A.,
RA   Damasio A.R., Diallinas G., Emri T., Fekete E., Flipphi M., Freyberg S.,
RA   Gallo A., Gournas C., Habgood R., Hainaut M., Harispe M.L., Henrissat B.,
RA   Hilden K.S., Hope R., Hossain A., Karabika E., Karaffa L., Karanyi Z.,
RA   Krasevec N., Kuo A., Kusch H., LaButti K., Lagendijk E.L., Lapidus A.,
RA   Levasseur A., Lindquist E., Lipzen A., Logrieco A.F., MacCabe A.,
RA   Maekelae M.R., Malavazi I., Melin P., Meyer V., Mielnichuk N., Miskei M.,
RA   Molnar A.P., Mule G., Ngan C.Y., Orejas M., Orosz E., Ouedraogo J.P.,
RA   Overkamp K.M., Park H.-S., Perrone G., Piumi F., Punt P.J., Ram A.F.,
RA   Ramon A., Rauscher S., Record E., Riano-Pachon D.M., Robert V., Roehrig J.,
RA   Ruller R., Salamov A., Salih N.S., Samson R.A., Sandor E., Sanguinetti M.,
RA   Schuetze T., Sepcic K., Shelest E., Sherlock G., Sophianopoulou V.,
RA   Squina F.M., Sun H., Susca A., Todd R.B., Tsang A., Unkles S.E.,
RA   van de Wiele N., van Rossen-Uffink D., Oliveira J.V., Vesth T.C.,
RA   Visser J., Yu J.-H., Zhou M., Andersen M.R., Archer D.B., Baker S.E.,
RA   Benoit I., Brakhage A.A., Braus G.H., Fischer R., Frisvad J.C.,
RA   Goldman G.H., Houbraken J., Oakley B., Pocsi I., Scazzocchio C.,
RA   Seiboth B., vanKuyk P.A., Wortman J., Dyer P.S., Grigoriev I.V.;
RT   "Comparative genomics reveals high biological diversity and specific
RT   adaptations in the industrially and medically important fungal genus
RT   Aspergillus.";
RL   Genome Biol. 18:RESEARCH28.1-RESEARCH28.45(2017).
RN   [2]
RP   FUNCTION, DOMAIN, DISRUPTION PHENOTYPE, PATHWAY, AND INDUCTION.
RX   PubMed=32234543; DOI=10.1016/j.fgb.2020.103378;
RA   Wolff P.B., Nielsen M.L., Slot J.C., Andersen L.N., Petersen L.M.,
RA   Isbrandt T., Holm D.K., Mortensen U.H., Noedvig C.S., Larsen T.O.,
RA   Hoof J.B.;
RT   "Acurin A, a novel hybrid compound, biosynthesized by individually
RT   translated PKS- and NRPS-encoding genes in Aspergillus aculeatus.";
RL   Fungal Genet. Biol. 139:103378-103378(2020).
CC   -!- FUNCTION: Nonribosomal peptide synthetase; part of the cluster that
CC       mediates the biosynthesis of acurin A, a highly reduced polyketide
CC       coupled to a serine via a peptide bond (PubMed:32234543). The
CC       activities of the highly reducing polyketide synthase acrA and the
CC       nonribosomal peptide synthetase acrB are collectively responsible for
CC       the synthesis of the acurin A core structure with a heptaketide
CC       backbone produced by acrA covalently fused to a L-serine by acrB
CC       (PubMed:32234543). After the formation of the PK-NRP hybrid product, it
CC       is detached from acrB by reductive release to set up the formation of
CC       the lactam ring by aldol condensation (Probable). The hydrolyase acrC
CC       then catalyzes water loss to generate a double bond in the ring
CC       (Probable). This double bond is probably reduced, which is followed by
CC       three oxidations at C-22 to generate the carboxylic acid moiety,
CC       involving probably the FAD-binding monooxygenase acrE and the
CC       cytochrome P450 monooxygenases acrD and acrF (Probable). Finally, a
CC       last methylation step performed by the O-methyltransferase acrG leads
CC       to the production of acurin A (Probable). {ECO:0000269|PubMed:32234543,
CC       ECO:0000305|PubMed:32234543}.
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:32234543}.
CC   -!- INDUCTION: Expression is positively regulated by the acurin A cluster-
CC       specific transcription regulator acrR. {ECO:0000269|PubMed:32234543}.
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. AcrB has the following architecture:
CC       C-A-T-TE. {ECO:0000305|PubMed:32234543}.
CC   -!- DISRUPTION PHENOTYPE: Abolishes the production of acurin A.
CC       {ECO:0000269|PubMed:32234543}.
CC   -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
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DR   EMBL; KV878980; OJJ98497.1; -; Genomic_DNA.
DR   RefSeq; XP_020054837.1; XM_020196524.1.
DR   AlphaFoldDB; A0A1L9WR63; -.
DR   SMR; A0A1L9WR63; -.
DR   STRING; 690307.A0A1L9WR63; -.
DR   EnsemblFungi; OJJ98497; OJJ98497; ASPACDRAFT_122295.
DR   GeneID; 30970338; -.
DR   VEuPathDB; FungiDB:ASPACDRAFT_122295; -.
DR   OrthoDB; 527862at2759; -.
DR   Proteomes; UP000184546; Unassembled WGS sequence.
DR   GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR   GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR   GO; GO:0009058; P:biosynthetic process; IEA:UniProt.
DR   Gene3D; 1.10.1200.10; -; 1.
DR   Gene3D; 3.30.300.30; -; 1.
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; IPR025110; AMP-bd_C.
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; IPR020806; PKS_PP-bd.
DR   InterPro; IPR009081; PP-bd_ACP.
DR   Pfam; PF00501; AMP-binding; 1.
DR   Pfam; PF13193; AMP-binding_C; 1.
DR   Pfam; PF00668; Condensation; 1.
DR   Pfam; PF07993; NAD_binding_4; 1.
DR   Pfam; PF00550; PP-binding; 1.
DR   SMART; SM00823; PKS_PP; 1.
DR   SUPFAM; SSF47336; SSF47336; 1.
DR   SUPFAM; SSF51735; SSF51735; 1.
DR   TIGRFAMs; TIGR01733; AA-adenyl-dom; 1.
DR   PROSITE; PS00455; AMP_BINDING; 1.
DR   PROSITE; PS50075; CARRIER; 1.
PE   2: Evidence at transcript level;
KW   Ligase; Multifunctional enzyme; Phosphopantetheine; Phosphoprotein;
KW   Reference proteome.
FT   CHAIN           1..1552
FT                   /note="Nonribosomal peptide synthetase acrB"
FT                   /id="PRO_0000450423"
FT   DOMAIN          1110..1186
FT                   /note="Carrier"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT                   ECO:0000305|PubMed:32234543"
FT   REGION          129..564
FT                   /note="Condensation"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:32234543"
FT   REGION          594..999
FT                   /note="Adenylation"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:32234543"
FT   REGION          1226..1464
FT                   /note="Thiolester reductase (R) domain"
FT                   /evidence="ECO:0000255, ECO:0000305|PubMed:32234543"
FT   MOD_RES         1146
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ   SEQUENCE   1552 AA;  170280 MW;  DA65745A1364BACE CRC64;
     MIMTANNDMA VRESVVVTEG ASSTPELWQM LGSRDQPTNI TPRVRITDVD HKQLHSSANL
     VSARALQQLT KSLHEGICST ALEDDSQSSS AYYSTYASTP RSLSPNLEAV PSDDGIPDLQ
     PQFEAVERAS FAQERIWFLH EYLTDPTTFN VTMAYAVQGP LQPAELATAF RAMSDRHESL
     RTAFFLDSRD GEPQLFQGIL PETQIEISIH TIDSTQVVDE VYASVRDHVY DLPRGKTMKV
     AILTLTPTTH FLVLGFHHIA LDGFSAQIFI KDLQLIYSTG QILPPAPRYR DYTLLQRQSL
     ANDTYRESLD FWKSKLANLP PPMPLFAFSR VAARKPLNSY RVHSVERTIG ISLASKIKDT
     AHKVGGTTSF FLYLTALREL VFRLLGHAQR DICLGISDAG RADKEALQVV GMFVNMLPLQ
     FRAARPGQSF RDLLATTTRQ VRTALTHAAV PYQVLLDELA VQRSPSENPL FQILLNYKMG
     STEEATLGHC RAHSLRMDDA RTGLDLVIEV EEFVDGNFQV AVRGQEYLYG EEGLEFILSS
     LVTILEEVTL RPSMPVANLA IFDEKSITHA LELSRGEHVF TAEHLLTVVH LFDRHCKAHP
     RDVAVKQADG QFLSYGELQG RAQELARRLQ ELEGSTAVVV ACKPSLDTIV SIVGIHYAGC
     TYVPVDIEHP EERLRTIVED CKPRAILYHA DTQDLAVALA GGAIAVPTPQ SGMDKAFPIK
     ASVNDTAYIL YTSGSTGKPK GVIVSHGNLT CQILSMRRTA TLGKETVLHQ SGVAFDASID
     CVYAALAGQG TLVMAPPEVR RDPVQLASLM AREQITYTQM TSSEYHNLVV YGAEHLKQCV
     TYRNAFCGGE KFLSSLIPLF RALELPALRV WNRYGPTEIT VSSSMQMIVG ADGLNRSTEL
     IPCGRPLTNY SVFILDEQRR PVPAGVPGEI CIGGGGVAQG YLNNARLTAS KFVKNIYASE
     DDVRRGWDRL YRTGDRGYLL SDGSLVFLGR MEGSAQVKIR GQRVELDEIE TAIVATSEGR
     VLSAGVCVKG DNADAVLAAY VVLRPDVQVD SLSSLVASLA RSLPLPRYMR PSSFVAVGRL
     PHNTSGKLDR QALSKLSGTP IAIETNNHPA PLGVEEEVMA KAWREVLPGE AVLSAESNFF
     DVGGNSLLLV RLQKVIEELT GKSVALTELF STPGMSAMAR LLQPQEATRE TTEVDWESET
     QLTPSLLSAI QTSSRCSPSS EVEVILTGAT GFLGRTLLQQ LLAHPRIAHV HCLAIRNSSV
     TRASLTSNPD HAAKLTLYHG DLSHPTLSLN EETISSLSNR IGLVIHNGAS VSFLKSYSTL
     RAPNVHSSRF LLQLSIERGI PFHFVSTGGV VNLTGQPTWP PVSVRNYPPP GEQGYIASKW
     ASERLIENAA EALHLRGVHL PVVVHRPASI VARQPGTPGT SQSEPPAMDI MHNMVQYARI
     MQCFPATEGV NWRFDFVGVD AVASGILASA LGEEDESEGV KYVHHCNERK LSPRELKKEL
     EEEAGCVFEE VEVGEWVRRA KECGMDGLVA ATLVDLMERQ RGVVFTEMGL DC