BUAA_ASPBU
ID BUAA_ASPBU Reviewed; 3987 AA.
AC A0A411L027;
DT 11-DEC-2019, integrated into UniProtKB/Swiss-Prot.
DT 08-MAY-2019, sequence version 1.
DT 03-AUG-2022, entry version 16.
DE RecName: Full=Hybrid PKS-NRPS synthetase buaA {ECO:0000303|PubMed:30735051};
DE EC=2.3.1.- {ECO:0000269|PubMed:30735051};
DE EC=6.3.2.- {ECO:0000269|PubMed:30735051};
DE AltName: Full=Burnettramic acids biosynthesis cluster protein A {ECO:0000303|PubMed:30735051};
GN Name=buaA {ECO:0000303|PubMed:30735051};
OS Aspergillus burnettii.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus.
OX NCBI_TaxID=2508778;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DOMAIN, AND PATHWAY.
RC STRAIN=FRR 5400;
RX PubMed=30735051; DOI=10.1021/acs.orglett.8b04042;
RA Li H., Gilchrist C.L.M., Lacey H.J., Crombie A., Vuong D., Pitt J.I.,
RA Lacey E., Chooi Y.H., Piggott A.M.;
RT "Discovery and Heterologous Biosynthesis of the Burnettramic Acids: Rare
RT PKS-NRPS-Derived Bolaamphiphilic Pyrrolizidinediones from an Australian
RT Fungus, Aspergillus burnettii.";
RL Org. Lett. 21:1287-1291(2019).
CC -!- FUNCTION: Hybrid PKS-NRPS synthetase; part of the gene cluster that
CC mediates the biosynthesis of burnettramic acids, an unusual class of
CC bolaamphiphilic pyrrolizidinediones that display potent antibacterial,
CC antifungal, and cytotoxic activities (PubMed:30735051). The first step
CC of the biosynthesis of burnettramic acids is the hydroxylation of
CC proline by the proline hydroxylase buaE to generate 4-hydroxyproline
CC (PubMed:30735051). The PKS-NRPS buaA and trans-enoyl reductase buaC
CC construct the highly reduced polyketide chain, and the condensation (C)
CC domain of buaA then catalyzes the amide bond formation with the
CC activated 4-hydroxyproline (PubMed:30735051). This is followed by the R
CC domain releasing the nascent polyketide-peptide directly via a
CC Dieckmann condensation to afford a tetramic acid fused to the
CC hydroxyproline, generating the bicyclic pyrrolidinedione moiety
CC (PubMed:30735051). The cytochrome P450 monooxygenases buaD and buaG are
CC likely responsible for the multiple hydroxylations on the polyketide
CC chain and its terminus, although in a heterologous context, buaD does
CC not appear to be required. Therefore, while buaG may be a
CC multifunctional cytochrome P450 monooxygenase, it cannot be ruled out
CC that the two secondary alcohols on the polyketide chain could have an
CC acetate origin (PubMed:30735051). Finally, the glycosyltransferase buaB
CC transfers beta-D-mannose to the aglycone burnettramic acid A to form
CC burnettramic acid A (PubMed:30735051). Burnettramic acid B is a minor
CC cis-pyrrolizidine epimer of burnettramic acid A and it is likely that
CC small amounts of it form naturally in acidic environments
CC (PubMed:30735051). {ECO:0000269|PubMed:30735051}.
CC -!- PATHWAY: Mycotoxin biosynthesis. {ECO:0000269|PubMed:30735051}.
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 (By similarity). BuaA contains
CC also a polyketide synthase module (PKS) consisting of several catalytic
CC domains including a ketoacyl synthase domain (KS), an acyl transferase
CC domain (AT), a dehydratase domain (DH), a methyltransferase domain
CC (MT), and a ketoreductase domain (KR) (Probable). Instead of a
CC thioesterase domain (TE), buaA finishes with a reductase-like domain
CC (R) for peptide release. BuaA has the following architecture: KS-AT-DH-
CC KR-PCP-C-A-T-R (Probable). {ECO:0000250|UniProtKB:Q4WAZ9,
CC ECO:0000305|PubMed:30735051}.
CC -!- SIMILARITY: In the C-terminal section; belongs to the NRP synthetase
CC family. {ECO:0000305}.
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DR EMBL; MK425157; QBE85649.1; -; Genomic_DNA.
DR SMR; A0A411L027; -.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0016874; F:ligase activity; IEA:UniProtKB-KW.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0017000; P:antibiotic biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR Gene3D; 1.10.1200.10; -; 2.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.30.300.30; -; 1.
DR Gene3D; 3.30.559.10; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.40.50.12780; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
DR InterPro; IPR010071; AA_adenyl_domain.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
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; IPR018201; Ketoacyl_synth_AS.
DR InterPro; IPR014031; Ketoacyl_synth_C.
DR InterPro; IPR014030; Ketoacyl_synth_N.
DR InterPro; IPR016036; Malonyl_transacylase_ACP-bd.
DR InterPro; IPR013217; Methyltransf_12.
DR InterPro; IPR036291; NAD(P)-bd_dom_sf.
DR InterPro; IPR032821; PKS_assoc.
DR InterPro; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR013968; PKS_KR.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR006162; Ppantetheine_attach_site.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF00501; AMP-binding; 1.
DR Pfam; PF00668; Condensation; 1.
DR Pfam; PF16197; KAsynt_C_assoc; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF08659; KR; 1.
DR Pfam; PF08242; Methyltransf_12; 1.
DR Pfam; PF07993; NAD_binding_4; 1.
DR Pfam; PF00550; PP-binding; 2.
DR Pfam; PF14765; PS-DH; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 2.
DR SUPFAM; SSF47336; SSF47336; 2.
DR SUPFAM; SSF51735; SSF51735; 2.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR TIGRFAMs; TIGR01733; AA-adenyl-dom; 1.
DR PROSITE; PS00455; AMP_BINDING; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 2.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 3: Inferred from homology;
KW Antibiotic biosynthesis; Ligase; Methyltransferase; Multifunctional enzyme;
KW Oxidoreductase; Phosphopantetheine; Phosphoprotein; Repeat; Transferase.
FT CHAIN 1..3987
FT /note="Hybrid PKS-NRPS synthetase buaA"
FT /id="PRO_0000448729"
FT DOMAIN 2397..2473
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 3564..3644
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 8..441
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000250|UniProtKB:Q5SBL6, ECO:0000255"
FT REGION 546..872
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 940..1238
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000255"
FT REGION 1399..1583
FT /note="Methyltransferase (MT) domain"
FT /evidence="ECO:0000255"
FT REGION 2113..2285
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255"
FT REGION 2489..2561
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2582..3001
FT /note="Condensation (C) domain"
FT /evidence="ECO:0000255"
FT REGION 3042..3448
FT /note="Adenylation (A) (KR) domain"
FT /evidence="ECO:0000255"
FT REGION 3680..3916
FT /note="Reductase (R) domain"
FT /evidence="ECO:0000255"
FT COMPBIAS 2528..2555
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 176
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2433
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 3604
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 3987 AA; 438850 MW; 4877E716F4BBA2B1 CRC64;
MAPQNEPIAI VGSGCRFPGE ASSPSKLWDL LREPRDVLSK IDRFSADGFY NKDGHHHGSS
NVLHSYQLSE DTRSFDAQFF NIPASEAESM DPQQRFIMEV VYEALESAAI KIEELSGSPT
AVYVGVMCND YAHITYADLE SVPKYAATGT ALSILANRIS YFFNWTGPSM TIDTACSSSL
VALHHAVQTL RGGTSKVAVA AGTNLIFTPT NYIAESNVNM LSPTGRSRMW DANADGYARG
EGVAAVVLKT LSQAVADGDR IECVIRETGL NQDGRTPGIT MPSSVAQAEL IRSTYARAGL
DVTRESDRPQ FFEAHGTGTK AGDPEEAKAI YKAFFGQEDT MDARDTLYVG SIKTIIGHTE
GTAGLAGLLK ASLAVQNKTL PPNMHFHTLN PDIEPYYGKL QILTSVKPWP ALASGVPRRV
SVNSFGFGGA NAHAIVESYE PSNGAIKVQS SKETAIPFTF SGYSEKSLMS QLTSFLEYLD
SHPEPRLRDS AWTLSRRSAF STRTTVSGTS IERLQEKLQS KIDSKIKDGK ALGIRSSSKN
DKILGVFTGQ GAQWPRMGLR LLQSSATARR IFDDLERSLA ELPTEDRPSW SLVQELEREA
EDSRVMEAEF SQVLCTAVQV MLVDLLHSVG VSFDIVVGHS SGEIGAAYSA GYLSARDAIR
IAYYRGKFGK LACGRDGVAG GMLAAGTDMA DAKDLCELDD FVGRLQLAAS NSSSSVTLSG
DAEAVAWAQF VLEDEKKFAR LLKVDTAYHS YHMQPCAEPY IEAMKRAGIQ ALKPQSDCRW
FSSVLEGQEV SAAMSASLAN SYWRDNLLQP VMFSQALEQA VSNTSDIGLV LEVGPHAALR
GPATLTINDK LGRDVPYFGL LSRNADDVES FSDGIGAVWA SLARCVIDFT RVDALLADGP
EDQPRLCDNV PGYSWDHQRT YWMESRSSAA LRLRPAAHHE LLGVRVDSLN REYRWRNFIK
PSQLSWTRGH QVQSQLIFPG AGFSVMALEA AKALAPAEKI ALVELTDMQV LRAMAFQDEN
TAVEVICSLS NVIEDPDQAN LTANFTCDMC LSKESGFVMA ACGAVRLQLG AASSQLLPER
TACPVRMNDV NIEHFYSTLW SLGYNYTDMF RSITSLQRTT DAASGIIHTT TEPDYTTSLT
LHPATLDVAF QGIFGAMGAP GDGRLWTVLV PTRIKRITIN PAVCGGTSGL GVDLPFDASV
SVSPIDGVAG DVDIFDSTGV NKAVQVEGLQ VAPLVPVTQS DDREVFSDTI WNFQEPDAAR
DVPKWTLTDE EWEHARYVER ACFYYLKQLH DTITAEERDR CEWHPRKMLD WATEVVGVVS
RGEHPIIRQE WMNDTWEMLK GPLDELTAKY EDFESLTHVG KNLIPFVKGE FSLLELVRNG
GLLEHIYRNT YAFCEYNNYL ANLVKQLSHR FPRMDIFEIG AGTGSTTEAV LRGIGDHYSS
YTYTDLSAGF FPNAQETFKE HDAKMIYKIY DAEKEPGKQG YTERTYDLVI ASNVLHATHS
LETTLTNARK LLKPGGYLVM LEVTDVNPLR PTFFFGCLPG WWVGENDGRP HHPLVTKERW
GELFDRTGFS GLDTSTPSHD VFMAPFSVML TQAVDRQMAL IRQPLQEDNR TTIDHLLILG
GTGFTSFMLI EDVKHQLKRY AKHVIVVETL EALEASHFHS RQMLLSLVEL DAPVFSPFTP
ERFAALQMLT EKCRNVLWVV RGASGEQPYA NMMNGVARCL VGEQPDMRFQ FVDFDMADKV
DAGFIVRSLL QLQISDAWHT FIEPYRPVWT LEREVRYIQG QAHIPRYSPS LRRNLQYNSW
RRTIRETVDP SSKYVILTHA NGYYDLEEDN SPRPDPMAED DRMAINVSRS STVAVEIDGI
GHLYILTGEC ELSGQRVLAF SSHNASRVQV KKDWVVSIGI LSSDEPALIQ MVTNVCLGTM
LLNQTPRNGS LLVYEPTVAL ARILTALTSA EEPGRVLFTT TNRAKLDSGV AFSFIHPSSP
DSSIARWVPA GVAGFVDASG GRKEQNMAAR FARHLSSQCR VISMEGFYSN SSHQWGNAGG
NSLSALLQHS TGLFTQGYKQ CKQNQVQELS LDDVIGASTE HKEIRILNWK SQSKALVKLS
PVQDEITFKG DRTYLLVGLT GELGRSLCRW MVQRGARYVV LTSRKPDVEP AWLELMQSYG
AHIEVMAMDA TDRKSTYNTV RKVQQTLPPV AGVGNGAMVL NDGLFNVISH QDFNQTLRPK
VDGTTYLNEL FQSPDLDFFI VFSSLAYVTG NFGQTSYAAA NAFMASLVEG RKRRGLPGSV
MNLAGIFGLG YITRTDRSIL ERLGKLGYAN ISEYDFHQFF AEAVLSGVPG SGRCHEISSA
LRPIDPDGET NPPAWLDMPR LSYYRHTKHA FTESGDTKSL SVRSQLKEQT TMEDVQRVLT
NGLILTLYKQ LGLDPEDDAI SPDTSLVELG IDSLVAVDMR VWFTKELDLD MPVLKLLGGA
TVAAMVEDTM ERMSPDLIPN VAQKDVTVAA DRPSAPSDGV PAVGRSTAVS TTEHNSEEQE
SHAMETQELD ESTTSGGECS STKESSSSEA TPPPSSVMSE DLAKVEETAS IDGPKYVRKV
KMGYGSLQFF FLVKHLDDPT VLNMQFRLPL QGSIKIPDLK YAVKMLGQRH EALRTAFFVD
AENDDEPTQG VLETSPLQLE TMQVTDSKEA RRVCEDVQKY VFNIESGETI RILLLSITPS
SHWLVLSFHH ISIDGFSFNI LLDEINALYQ GQHLPPVKTQ FTDVMCKQRQ DLQAGFRRSE
LAYWQQVLGK IPDPIPLFPV AKLSSRLPVT RYHFEEAPMA SIDAATAEQI RKQCRALKAT
RFHFFMTVLR IFLFAFLDTD ELCIGFADAS RADSGVSRTV GYLVNMLSLK FQRKPSQTFA
QKVEEARKQS YAALANSTVP FNALLEKLEP PRSAAYTPVF QVFMDYLQHK FTAPKGLGVV
EEQVYAHLTH NFFDLAVDIN DVSASEILVR FRMQQYLYSA SSVSLLLKSY VQLVKMCAYM
EPNKAIGEPV PYDAQDIERA ISLGQGPVVS SQWPSTPIER ILDVAQARPE APALVDGEGA
RLSYMEMIDR AHSIAGCLLT AGVAEGSTVG VYQEPTADSI CSLLAIWIIG AVYLPLDRRV
PCSRLSSIVQ DCQPSAILCH ERTLSDTPYL EATKQTAIIT VPVNVAGIEA APVPLNTGNG
DQTSIILYTS GSTGVPKGLP IRHVSLLNQI EAMTTTFGVG AEMVLQQSAP SFDVSMQQIL
MALCNGGALY VVPNETRLDP VTITRLIASE KITWVHATPS EFTQWLRHGS AHLRAAKDWK
FAFSSGEALS SDLVKGFEAL RRPDVKLINV YGPAEAGVIT GTEIDTTHVS AEPRSPISLG
SPLANIAVYV VDRNLRPVPV GVSGEIVVAG AGNISGYLNR FELTAKLFLP DTITPRGYYP
GQLATLYRSG DIGRYSPDGQ LYYEGRIAGD TQVKLNGIRI DLKDVESAIL ETSGGEIVNA
IVTDRRSPDF LVAHVELKAD FPEAERKNFL TYIQQCLPLP KYMCPAMFIP LDHVPLNSHG
KLDRRAIAAR PLPTVDGDDQ QGDADLSETE LALRELWTGC LPEDVVKLTS ISATTDFFHL
GGNSYLLVRL QRLIRDRFNV SVPVMALYDA STLMAMALKI RNSQSLAVID WDTETSVAQS
LGASPCAEQP TAPRKTTDLT VVLTGATGYL GSRIMKALIA SEQVSQIHCV AVRGHSAGVP
RELAHSSDKL ILHGGHLEDP LLGMSEEEFT FVARETDLVI HSGANRSFWD HYERLRGPNV
LSTKTLVDLA LQNQAPLHFI SSGGVHLLCS GEDYAAESLA SYLPPTDGSN GYIASKWASE
VYLEKAAQKT SLPVYVHRLT PAPDVTPDAP MELLEEMSAL AVKLQALPAP SGWTGTFDLT
PAEALATGIA AAAVGAQAPM LESHQSARFI HHPSQVKMTM DHVAKYLDML PSAEGFERLP
PLQWAGRAKR EGLTWHFSST DFITMGG
