ID   ANEB_ASPA1              Reviewed;        1078 AA.
AC   A0A1L9WUW3;
DT   26-FEB-2020, integrated into UniProtKB/Swiss-Prot.
DT   15-MAR-2017, sequence version 1.
DT   25-MAY-2022, entry version 25.
DE   RecName: Full=Nonribosomal peptide synthase aneB {ECO:0000303|PubMed:31618514};
DE            EC=6.2.1.53 {ECO:0000269|PubMed:31618514};
DE   AltName: Full=Aculenes biosynthesis cluster protein B {ECO:0000303|PubMed:31618514};
GN   Name=aneB {ECO:0000303|PubMed:31618514}; ORFNames=ASPACDRAFT_29371;
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, DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, AND PATHWAY.
RX   PubMed=31618514; DOI=10.1002/anie.201910200;
RA   Lee C.F., Chen L.X., Chiang C.Y., Lai C.Y., Lin H.C.;
RT   "The biosynthesis of norsesquiterpene aculenes requires three cytochrome
RT   P450 enzymes to catalyze a stepwise demethylation process.";
RL   Angew. Chem. Int. Ed. 58:18414-18418(2019).
CC   -!- FUNCTION: Nonribosomal peptide synthase; part of the gene cluster that
CC       mediates the biosynthesis of aculenes, a unique type of
CC       norsesquiterpenes that contain a nordaucane skeleton linked to an L-
CC       proline moiety and are of mixed biosynthetic origin (PubMed:31618514).
CC       The pathway begins with the synthesis of dauca-4,7-diene by the terpene
CC       cyclase aneC using farnesyl pyrophosphate (FPP) as substrate
CC       (PubMed:31618514). The cytochrome P450 monooxygenase aneF then performs
CC       the initial oxidation at C-12 of dauca-4,7-diene to yield asperaculane
CC       D (PubMed:31618514). Asperaculane D is substrate of the cytochrome P450
CC       monooxygenase aneD for C-10 hydroxylation to yield asperaculane E
CC       (PubMed:31618514). The cytochrome P450 monooxygenase aneG then converts
CC       asperaculane E into aculene D via C-2 oxidation (PubMed:31618514). The
CC       monomodular nonribosomal peptide synthase aneB adenylates L-proline and
CC       the thiohydrolase aneE transfers this activated L-proline derivative to
CC       aculenes D and C to produce respectively aculenes B and A
CC       (PubMed:31618514). The dioxygenase aneA converts aculene D into aculene
CC       C, and aculene B into aculene A by introducing the 5,6-alkene moiety
CC       (PubMed:31618514). Asperculanes A, B, C and F, as well as 14-prolyl
CC       asperculane C, might be shunt products of the pathway
CC       (PubMed:31618514). {ECO:0000269|PubMed:31618514}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + holo-[peptidyl-carrier protein] + L-proline = AMP +
CC         diphosphate + L-prolyl-[peptidyl-carrier protein];
CC         Xref=Rhea:RHEA:11656, Rhea:RHEA-COMP:11480, Rhea:RHEA-COMP:14109,
CC         ChEBI:CHEBI:30616, ChEBI:CHEBI:33019, ChEBI:CHEBI:60039,
CC         ChEBI:CHEBI:64479, ChEBI:CHEBI:138622, ChEBI:CHEBI:456215;
CC         EC=6.2.1.53; Evidence={ECO:0000269|PubMed:31618514};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:11657;
CC         Evidence={ECO:0000269|PubMed:31618514};
CC   -!- PATHWAY: Secondary metabolite biosynthesis.
CC       {ECO:0000269|PubMed:31618514}.
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 (Probable). AneB has a monomodular A-T-C architecture
CC       (Probable). {ECO:0000305, ECO:0000305|PubMed:31618514}.
CC   -!- DISRUPTION PHENOTYPE: Abolishes the production of aculenes A and B and
CC       accumulates aculenes C and D. {ECO:0000269|PubMed:31618514}.
CC   -!- SIMILARITY: Belongs to the NRP synthetase family. {ECO:0000305}.
CC   ---------------------------------------------------------------------------
CC   Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC   Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC   ---------------------------------------------------------------------------
DR   EMBL; KV878977; OJJ99913.1; -; Genomic_DNA.
DR   RefSeq; XP_020056253.1; XM_020199636.1.
DR   AlphaFoldDB; A0A1L9WUW3; -.
DR   SMR; A0A1L9WUW3; -.
DR   EnsemblFungi; OJJ99913; OJJ99913; ASPACDRAFT_29371.
DR   GeneID; 30973450; -.
DR   VEuPathDB; FungiDB:ASPACDRAFT_29371; -.
DR   OrthoDB; 4243at2759; -.
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   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; 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; IPR020806; PKS_PP-bd.
DR   InterPro; IPR009081; PP-bd_ACP.
DR   InterPro; IPR006162; Ppantetheine_attach_site.
DR   Pfam; PF00501; AMP-binding; 1.
DR   Pfam; PF00550; PP-binding; 1.
DR   SMART; SM00823; PKS_PP; 1.
DR   SUPFAM; SSF47336; SSF47336; 1.
DR   TIGRFAMs; TIGR01733; AA-adenyl-dom; 1.
DR   PROSITE; PS00455; AMP_BINDING; 1.
DR   PROSITE; PS50075; CARRIER; 1.
DR   PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE   1: Evidence at protein level;
KW   Ligase; Phosphopantetheine; Phosphoprotein; Reference proteome.
FT   CHAIN           1..1078
FT                   /note="Nonribosomal peptide synthase aneB"
FT                   /id="PRO_0000449091"
FT   DOMAIN          559..635
FT                   /note="Carrier"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT   REGION          20..417
FT                   /note="Adenylation"
FT                   /evidence="ECO:0000250|UniProtKB:Q5AUZ6, ECO:0000255"
FT   REGION          699..1013
FT                   /note="Condensation"
FT                   /evidence="ECO:0000255"
FT   MOD_RES         596
FT                   /note="O-(pantetheine 4'-phosphoryl)serine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ   SEQUENCE   1078 AA;  119429 MW;  D9BE8116557D6537 CRC64;
     MTLDDNPVPP TLPYTLHGVF QQNVLDRPDA SAVCAWDGDL TYRELDEKSS TLAHILRHRG
     VQDGALVALC FDHSLWTAVA MMAVSKAGGV WFFLEPKHPV NRLRQMCRSV QARMVLCSRS
     QASVAAELSD DQMEAPLSIE EAVLREEDPG PMDLEVVSPE RPAYVAFTSG STGSPKGAVM
     THQAAVTGVL HNAKPMQLDR TARILQFASF AFDISFLEHF WALLLGGCLC IPAPLDRQNN
     TIHAVQSLQV NWMFLTPTVA RLLEPPQLPS LRTLVLGGEP VTQADLDMWL PYVHLAGLYG
     PAECAVGIAV QPDYSRVESA NNVGPPFSVA CWIVSEQDPT QLAPRGAVGE LVVEGPSISE
     GYINAPEQTT RAYLTNPTWL PAARHSTKKL YRTGDLARVL DDGSLLFHGR KDTQVKINGQ
     RIELGEIEYH TRAVLGKEHL RSPPVVAEAM EVRGRALTVI AFYQVEGVCQ DLDHDGQDLF
     LPPDDGFVGR KQSYQSQLRD HLPEYMIPTS FIPVRGLPLT MSGKTDRKTL REKFAQLPSD
     RIKAYFVDGD GGSRSTEGMP TTPLERQMQE LWAATLKLEL EEVGRNDPWM SLGGESLAAM
     RLVARARKEG IAVTVPDIFR HKTIATLCQH VSVRPGPETI ESFPPFSLVQ CQQGSTGIEE
     LRHAAAQQCG LTPEAIEDLY PFTAMQEAVV IPPATIGVNY TLRLDVKLPA ELDLEQLMRA
     WDMVVAANSV LRMRVVRLPA DESETMVLAV TRPEIPMEPL FAERFAPGVD LWGLGKPLVR
     VGVAPGRLVM LIQHALYDGH SLGLIFRDLE QAYRGQPVAA VSYSPFVHWS TEWQDGSNKQ
     QYWREKFAGF DGRVCPPRVA DAGIGCMESQ HFWGSLNFRP DGFTVTSKIR VALAVVLSWH
     FDTCDIVLGG IYARRGAPIP GIMESPVPAS AILPDRIRLD PTQSLRANVD QDQENILTMM
     PYEGIRPSQV LDLSEAARAA SQFQTILAVQ QDNSSVYPEM FRDHEMGYYG PVTAHNLMMQ
     CFLSPDRASA RVSLRLSERT MQETTAWDRF LAHFEAVVDA IQEKPEIPVD RLRQHLGA