VDTA1_BYSSP
ID VDTA1_BYSSP Reviewed; 2276 AA.
AC A0A443HK81;
DT 16-OCT-2019, integrated into UniProtKB/Swiss-Prot.
DT 08-MAY-2019, sequence version 1.
DT 25-MAY-2022, entry version 15.
DE RecName: Full=Non-reducing polyketide synthase VdtA {ECO:0000303|PubMed:31304040};
DE Short=PKS VdtA {ECO:0000303|PubMed:31304040};
DE EC=2.3.1.- {ECO:0000269|PubMed:31045362};
DE AltName: Full=Viriditoxin biosynthesis cluster protein A {ECO:0000303|PubMed:31304040};
GN Name=VdtA {ECO:0000303|PubMed:31304040}; ORFNames=C8Q69DRAFT_480069;
OS Byssochlamys spectabilis (Paecilomyces variotii).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Thermoascaceae; Paecilomyces.
OX NCBI_TaxID=264951;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CBS 101075;
RX PubMed=30619145; DOI=10.3389/fmicb.2018.03058;
RA Urquhart A.S., Mondo S.J., Maekelae M.R., Hane J.K., Wiebenga A., He G.,
RA Mihaltcheva S., Pangilinan J., Lipzen A., Barry K., de Vries R.P.,
RA Grigoriev I.V., Idnurm A.;
RT "Genomic and genetic insights into a cosmopolitan fungus, Paecilomyces
RT variotii (Eurotiales).";
RL Front. Microbiol. 9:3058-3058(2018).
RN [2]
RP IDENTIFICATION, FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND
RP PATHWAY.
RX PubMed=31304040; DOI=10.1186/s40694-019-0072-y;
RA Urquhart A.S., Hu J., Chooi Y.H., Idnurm A.;
RT "The fungal gene cluster for biosynthesis of the antibacterial agent
RT viriditoxin.";
RL Fungal Biol. Biotechnol. 6:2-2(2019).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=31045362; DOI=10.1021/jacs.9b03354;
RA Hu J., Li H., Chooi Y.H.;
RT "Fungal dirigent protein controls the stereoselectivity of multicopper
RT oxidase-catalyzed phenol coupling in viriditoxin biosynthesis.";
RL J. Am. Chem. Soc. 141:8068-8072(2019).
CC -!- FUNCTION: Non-reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of viriditoxin, one of the 'classical'
CC secondary metabolites produced by fungi and that has antibacterial
CC activity (PubMed:31304040, PubMed:31045362). The first step is
CC performed by the polyketide synthase VdtA which condenses one acetyl-
CC CoA and 6 malonyl-CoA units to form the heptaketide monomer backbone of
CC viriditoxin (PubMed:31304040). The product of VdtA is then O-methylated
CC on C7 by the O-methyltransferase VdtC (PubMed:31304040,
CC PubMed:31045362). The O-methyl group is important for the
CC stereoselective coupling of the monomers at the final step of
CC viriditoxin biosynthesis (PubMed:31304040, PubMed:31045362). The short-
CC chain dehydrogenase/reductase VdtF then acts as a stereospecific
CC reductase converting the pyrone to dihydropyrone via the reduction of
CC the C3-C4 double bond (PubMed:31304040, PubMed:31045362). The FAD-
CC binding monooxygenase VdtE then converts the ketone group into a
CC methyl-ester group to yield semi-viriditoxin (PubMed:31304040,
CC PubMed:31045362). Finally, the laccase VdtB is involved in dimerization
CC of 2 semi-viriditoxin molecules to yield the final viriditoxin
CC (PubMed:31304040, PubMed:31045362). VdtB is responsible for the
CC regioselective 6,6'-coupling of semi-viriditoxin, which yields (M)-
CC viriditoxin and (P)-viriditoxin at a ratio of 1:2 (PubMed:31304040,
CC PubMed:31045362). The non-catalytic carboxylesterase-like protein VdtD
CC affects the stereochemistical outcome of the coupling (PubMed:31304040,
CC PubMed:31045362). The highly reducing polyketide synthase VdtX is not
CC involved in viriditoxin synthesis, but might possibly play a role in
CC the production of additional metabolites not identified yet
CC (PubMed:31304040, PubMed:31045362). {ECO:0000269|PubMed:31045362,
CC ECO:0000269|PubMed:31304040}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + 7 H(+) + 7 malonyl-CoA = 7,9,10-trihydroxy-3-(2-
CC oxopropyl)-1H-benzo[g]isochromen-1-one + 7 CO2 + 8 CoA + 2 H2O;
CC Xref=Rhea:RHEA:62860, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:16526, ChEBI:CHEBI:57287, ChEBI:CHEBI:57288,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:146009;
CC Evidence={ECO:0000269|PubMed:31045362};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:62861;
CC Evidence={ECO:0000269|PubMed:31045362};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:31045362, ECO:0000269|PubMed:31304040}.
CC -!- SUBCELLULAR LOCATION: Cytoplasmic vesicle
CC {ECO:0000269|PubMed:31304040}. Note=The vesicles where VdtA is targeted
CC remain unknown. {ECO:0000269|PubMed:31304040}.
CC -!- DOMAIN: Multidomain protein; including a starter unit:ACP transacylase
CC (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes
CC repeated decarboxylative condensation to elongate the polyketide
CC backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and
CC transfers the extender unit malonyl-CoA; a product template (PT) domain
CC that controls the immediate cyclization regioselectivity of the
CC reactive polyketide backbone; and 3 acyl-carrier protein (ACP) domains
CC that serve as the tether of the growing and completed polyketide via
CC its phosphopantetheinyl arm. {ECO:0000305|PubMed:31304040}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of viriditoxin.
CC {ECO:0000269|PubMed:31304040}.
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DR EMBL; RCNU01000014; RWQ92175.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A443HK81; -.
DR SMR; A0A443HK81; -.
DR Proteomes; UP000283841; Unassembled WGS sequence.
DR GO; GO:0031410; C:cytoplasmic vesicle; IEA:UniProtKB-KW.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR Gene3D; 1.10.1200.10; -; 3.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 2.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.40.50.1820; -; 1.
DR InterPro; IPR029058; AB_hydrolase.
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; 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; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR030918; PT_fungal_PKS.
DR InterPro; IPR032088; SAT.
DR InterPro; IPR001031; Thioesterase.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF00550; PP-binding; 3.
DR Pfam; PF14765; PS-DH; 1.
DR Pfam; PF16073; SAT; 1.
DR Pfam; PF00975; Thioesterase; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 2.
DR SUPFAM; SSF47336; SSF47336; 3.
DR SUPFAM; SSF52151; SSF52151; 2.
DR SUPFAM; SSF53474; SSF53474; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR TIGRFAMs; TIGR04532; PT_fungal_PKS; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 3.
PE 1: Evidence at protein level;
KW Cytoplasmic vesicle; Multifunctional enzyme; Phosphopantetheine;
KW Phosphoprotein; Reference proteome; Repeat; Transferase.
FT CHAIN 1..2276
FT /note="Non-reducing polyketide synthase VdtA"
FT /id="PRO_0000448341"
FT DOMAIN 1655..1729
FT /note="Carrier 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 1765..1839
FT /note="Carrier 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT DOMAIN 1886..1964
FT /note="Carrier 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 8..243
FT /note="N-terminal acylcarrier protein transacylase (SAT)
FT domain"
FT /evidence="ECO:0000255"
FT REGION 375..807
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 905..1206
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 1300..1616
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255"
FT REGION 1735..1762
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1840..1882
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1967..1993
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2020..2271
FT /note="Thioesterase (TE) domain"
FT /evidence="ECO:0000255"
FT COMPBIAS 1743..1757
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1840..1856
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1858..1872
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 544
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 996
FT /note="For acyl/malonyl transferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 1689
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 1799
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MOD_RES 1923
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2276 AA; 249146 MW; 2D20E2F0138EC9E3 CRC64;
MAQKLRFYLF GDQTYDYDEQ LRALLTSHDP VVRSFLERAY YTLRAEVARI PNGYQARISR
FSSIAELLSQ RREHGVDASL EQALTVVYQL ASFMRLHSER SLSYPSADDA HCLGLCTGAL
SAAAVSSSRS LSELLPAAIE TVILAFRTGL HASDSGRRIE ESSAAAKCWS ISLQGLEGHV
ARKLLEEWSN KKRLPPMSRP YISAYASGGV TISGPPSVLA ELRNTPGLSK LRAKDIPIHA
PYHSSAIFNQ CDVETILSSA LIDLASRATH VPILSTGTGR LVWAGTLPAA IQSALQDVLL
RPISWENMSC GISTCLQSID PSEVEVIPIA TLAGPLLCRS VQVAKSQIPA TIDPKNDVMN
EAQSQIAEAM DRAKIAIVGM SGRFPGAENV DSLWELLMAG RDMCKEVPPT RWNVDTHVDP
TGKRKNTSKI RWGCWLDNPD MFDARFFNMS PREAPQVDPA QRIALITAYE AIEQAGIVPG
RTPSTQEDRV GVFFGTTSND WCESNSGQDI DTYYIPGANR AFIPGRINYV FKFSGPSYSI
DTACSSSLSA LHVACNALWH GDIDTAIAGG TNVLTNPDMT AGLDRGHFLS ATGNCKTFDD
TADGYCRGEG VATVVLKRMD DAIADKDPIL GVIRGVYTNH SAEAESITRP HVGAQKAIFQ
HVLNHSGIRP QDISYIEMHG TGTQAGDMRE MTSVLDTFSP QYPGAIQREK PLYLGAVKSN
IGHGESVSGV TALVKVIMMM QNNTIPPHRG VHTRLNRRFP SNLDERNVHI AFQATEWPRG
QTPRRAFINN FSAAGGNSSV LVEDPPLILK EEGADPRSSH VIAVSAKSPS ALRKNLESMR
RYAMSEHTEK SLCELSYTTT ARRIHHSHRL MFAGSSLEDI LREMESKLAI KEPFSPCAPL
QSVIFTFTGQ GAQYPGMGQV FFNNFSVFRS DLCRLDDLAQ KLGFPTFLPI FSASTHARLE
GFTPTVVQLA NTCMQLALTR LWVSWGIRPS AVVGHSIGEY AALNTAGVLS DADTVYLVGK
RAQLLEEKCN RGSHTMLAAL ASFEKVSRLL DSAPCEVACI NGPEEIVLAG PRSHMTDIQK
ILVAHSIRCT MLQVPFAFHS SQVDPILQDF QSAIEGVTFH KPTIPVISPL LGDFVTETGT
FNPNYLARHC REPVNILQAL RQASTMNLVH DSSVVMEFGP HPVVSGMVKS TLGNSIKALP
TLQRNRNTWE VLTESVSTLY CMGFDINWTE YHRDFPSSQR VLRLPSYSWD LKSYWIPYRN
DWTLYKGDIV PESSIALPTH QNKPHSTSPK QQAPTPILET TTLHRIVDEK STEGTFSITC
ESDVSRPDLS PLVQGHKVEG IGLCTPSVYA DIGFTLGNYL LDRFPTRFGP DTKVVDVTDM
VIEKALMPLN AGPQLLRVTA SLIWSEKEAS VRFYSVDENH TETVQHSHCR IKFSDRSTYQ
AYQEQISAVK ARMFEMKTNS SSGRTYRFNG PMAYNMVQAL AEFHPDYRCI DETILDNETL
EAACTVSFGN VKKEGVFHTH PGYIDGLTQS GGFVMNANDK TNLGVEVFVN HGWDSFQLYE
PVTDDRSYQT HVRMRPAESN QWKGDVVVLS GENLVACVRG LTIQGVPRRV LRYILQSSAK
TTQTATSSVP APSQAPVMVP QIVQVPKAKP ISQISGTLTE ALRIICEQSG VPLAELTDDA
TFANIGVDSL LALTITSAFV EELDLDVDSS LFMDYPTVAD LKRFFDKINT QHAPAPAPVS
DAPKQLQPSS SPVASATPSA PIHGRSKFES VLNILTEESG VEMAGLPDST ALADIGIDSL
LSLVVTSRLN DELELDVSSE DFNDCLTIRD LKAHFMSKNS DNGSSAVLTP QPSRDSALPE
RTRPRVADTS DEEDAPVSAN EFTTSARSTS KYMAVLNIIS EESGMAIEDF TDNVMFADIG
IDSLLSLVIG GRIREELSFD LEVDSLFVDY PDVKGLRSFF GFESNKTATN PTASQSSSSI
SSGTSVFDTS PSPTDLDILT PESSLSQEEF EQPLTIATKP LPPATSVTLQ GLPSKAHKIL
FLFPDGSGSA TSYAKLPRLG ADVAIIGLNS PYLMDGANMT CTFDELVTLY LTEIQRRQPA
GPYHLGGWSA GGILAYRAAQ ILQKAAANPQ KPVVESLLLL DSPPPTGLGK LPKHFFDYCD
QIGIFGQGTA KAPEWLITHF QGTNSVLHEY HATPFSFGTA PRTGIIWASQ TVFETRAVAP
PPVRPDDTED MKFLTERRTD FSAGSWGHMF PGTEVLIETA YGADHFSLLV SLLFRD
