SDGA_EMENI
ID SDGA_EMENI Reviewed; 2510 AA.
AC A0A1U8QN18; C8VPE2; Q5BCE6;
DT 10-FEB-2021, integrated into UniProtKB/Swiss-Prot.
DT 10-MAY-2017, sequence version 1.
DT 03-AUG-2022, entry version 27.
DE RecName: Full=Highly reducing polyketide synthase sdgA {ECO:0000303|PubMed:30302871};
DE Short=HR-PKS aurvA {ECO:0000303|PubMed:30302871};
DE EC=2.3.1.- {ECO:0000269|PubMed:30302871};
DE AltName: Full=Aspernidgulenes biosynthesis cluster protein A {ECO:0000303|PubMed:30302871};
GN Name=sdgA {ECO:0000303|PubMed:30302871}; ORFNames=AN1784, ANIA_01784;
OS Emericella nidulans (strain FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 /
OS M139) (Aspergillus nidulans).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Nidulantes.
OX NCBI_TaxID=227321;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=16372000; DOI=10.1038/nature04341;
RA Galagan J.E., Calvo S.E., Cuomo C., Ma L.-J., Wortman J.R., Batzoglou S.,
RA Lee S.-I., Bastuerkmen M., Spevak C.C., Clutterbuck J., Kapitonov V.,
RA Jurka J., Scazzocchio C., Farman M.L., Butler J., Purcell S., Harris S.,
RA Braus G.H., Draht O., Busch S., D'Enfert C., Bouchier C., Goldman G.H.,
RA Bell-Pedersen D., Griffiths-Jones S., Doonan J.H., Yu J., Vienken K.,
RA Pain A., Freitag M., Selker E.U., Archer D.B., Penalva M.A., Oakley B.R.,
RA Momany M., Tanaka T., Kumagai T., Asai K., Machida M., Nierman W.C.,
RA Denning D.W., Caddick M.X., Hynes M., Paoletti M., Fischer R., Miller B.L.,
RA Dyer P.S., Sachs M.S., Osmani S.A., Birren B.W.;
RT "Sequencing of Aspergillus nidulans and comparative analysis with A.
RT fumigatus and A. oryzae.";
RL Nature 438:1105-1115(2005).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=FGSC A4 / ATCC 38163 / CBS 112.46 / NRRL 194 / M139;
RX PubMed=19146970; DOI=10.1016/j.fgb.2008.12.003;
RA Wortman J.R., Gilsenan J.M., Joardar V., Deegan J., Clutterbuck J.,
RA Andersen M.R., Archer D., Bencina M., Braus G., Coutinho P., von Dohren H.,
RA Doonan J., Driessen A.J., Durek P., Espeso E., Fekete E., Flipphi M.,
RA Estrada C.G., Geysens S., Goldman G., de Groot P.W., Hansen K.,
RA Harris S.D., Heinekamp T., Helmstaedt K., Henrissat B., Hofmann G.,
RA Homan T., Horio T., Horiuchi H., James S., Jones M., Karaffa L.,
RA Karanyi Z., Kato M., Keller N., Kelly D.E., Kiel J.A., Kim J.M.,
RA van der Klei I.J., Klis F.M., Kovalchuk A., Krasevec N., Kubicek C.P.,
RA Liu B., Maccabe A., Meyer V., Mirabito P., Miskei M., Mos M., Mullins J.,
RA Nelson D.R., Nielsen J., Oakley B.R., Osmani S.A., Pakula T., Paszewski A.,
RA Paulsen I., Pilsyk S., Pocsi I., Punt P.J., Ram A.F., Ren Q., Robellet X.,
RA Robson G., Seiboth B., van Solingen P., Specht T., Sun J.,
RA Taheri-Talesh N., Takeshita N., Ussery D., vanKuyk P.A., Visser H.,
RA van de Vondervoort P.J., de Vries R.P., Walton J., Xiang X., Xiong Y.,
RA Zeng A.P., Brandt B.W., Cornell M.J., van den Hondel C.A., Visser J.,
RA Oliver S.G., Turner G.;
RT "The 2008 update of the Aspergillus nidulans genome annotation: a community
RT effort.";
RL Fungal Genet. Biol. 46:S2-13(2009).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=30302871; DOI=10.1002/cbic.201800486;
RA Lin T.S., Chen B., Chiang Y.M., Wang C.C.C.;
RT "Discovery and elucidation of the biosynthesis of aspernidgulenes: novel
RT polyenes from Aspergillus nidulans by using serial promoter replacement.";
RL ChemBioChem 20:329-334(2019).
CC -!- FUNCTION: Highly reducing polyketide synthase (HR-PKS); part of the
CC gene cluster that mediates the biosynthesis of the polyenes
CC aspernidgulenes (PubMed:30302871). The carbon backbone of
CC aspernidgulenes is synthesized by the HR-PKS sdgA, which accepts
CC acetyl-CoA as the starter unit and performs malonyl-CoA extensions as
CC well as regioselective methylation and reduction (PubMed:30302871). The
CC resulting nonaketide offloads the HR-PKS by intramolecular
CC lactonization to yield the 5,6-dihydro-alpha-pyrone-containing
CC hexaenoic acids preaspernidgulene A1 and A2 (PubMed:30302871). The FAD-
CC dependent monooxygenase sdgC then installs the first epoxide on the
CC penultimate double bond (PubMed:30302871). Subsequently, the FAD-
CC dependent monooxygenase sdgF presumably generates a ketone intermediate
CC through Meinwald rearrangement involving a hydride shift
CC (PubMed:30302871). Next, sdgC introduces another epoxide on the last
CC olefin of the ketone intermediate after E/Z isomerization
CC (PubMed:30302871). The epoxide hydrolase sdgD then catalyzes
CC stereospecific cyclization of the 5,6-dihydro-alpha-pyrone and opening
CC of the epoxide ring to form an oxygenated trimethylcyclopentanone and
CC an oxabicyclo[2.2.1]heptane unit (PubMed:30302871). Finally, the
CC bicyclic unit undergoes hydrolytic cleavage, either spontaneously or
CC catalyzed by sdgD, to assemble the dimethyl-gamma-lactone moiety in
CC aspernidgulene A1 (PubMed:30302871). {ECO:0000269|PubMed:30302871}.
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000250|UniProtKB:Q9Y8A5};
CC Note=Binds 1 phosphopantetheine covalently.
CC {ECO:0000250|UniProtKB:Q9Y8A5};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:30302871}.
CC -!- DOMAIN: Multidomain protein; including a ketosynthase (KS) that
CC catalyzes repeated decarboxylative condensation to elongate the
CC polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects
CC and transfers the extender unit malonyl-CoA; a dehydratase (DH) domain
CC that reduces hydroxyl groups to enoyl groups; a methyltransferase
CC (CMeT) domain responsible for the incorporation of methyl groups; a
CC ketoreductase (KR) domain that catalyzes beta-ketoreduction steps; and
CC an acyl-carrier protein (ACP) that serves as the tether of the growing
CC and completed polyketide via its phosphopantetheinyl arm.
CC {ECO:0000305|PubMed:30302871}.
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DR EMBL; BN001307; CBF85555.1; -; Genomic_DNA.
DR EMBL; AACD01000028; EAA63960.1; -; Genomic_DNA.
DR RefSeq; XP_659388.1; XM_654296.1.
DR AlphaFoldDB; A0A1U8QN18; -.
DR SMR; A0A1U8QN18; -.
DR STRING; 162425.CADANIAP00008431; -.
DR EnsemblFungi; CBF85555; CBF85555; ANIA_01784.
DR EnsemblFungi; EAA63960; EAA63960; AN1784.2.
DR GeneID; 2875011; -.
DR KEGG; ani:AN1784.2; -.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_31_0_1; -.
DR OMA; GGFEGWW; -.
DR OrthoDB; 19161at2759; -.
DR Proteomes; UP000000560; Chromosome VII.
DR Proteomes; UP000005890; Unassembled WGS sequence.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
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; -; 1.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 3.40.50.150; -; 1.
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; 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; PF16197; KAsynt_C_assoc; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 2.
DR Pfam; PF08659; KR; 1.
DR Pfam; PF08242; Methyltransf_12; 1.
DR Pfam; PF00550; PP-binding; 1.
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; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF51735; SSF51735; 1.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
PE 1: Evidence at protein level;
KW Methyltransferase; Multifunctional enzyme; Phosphopantetheine;
KW Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..2510
FT /note="Highly reducing polyketide synthase sdgA"
FT /id="PRO_0000451913"
FT DOMAIN 2416..2494
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 11..468
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 579..896
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 965..1257
FT /note="Dehydrogenase (DH) domain"
FT /evidence="ECO:0000255"
FT REGION 1397..1592
FT /note="Methyltransferase (CMet) domain"
FT /evidence="ECO:0000255"
FT REGION 2123..2297
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255"
FT ACT_SITE 181
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 181
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 671
FT /note="For malonyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 997
FT /note="For beta-hydroxyacyl dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2454
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2510 AA; 273179 MW; 894DEA8755058FD0 CRC64;
MAYDNTVVEP IAIIGTGCRL PGGSSSPSRL WTLLKNPRVV ASETPGDRFD INAFYHEDPG
YPGTTNSKEA YYISDDPRPF DAPFFNISAT EAESIDPQQR QLLETVYESL ESAGLRLDAL
QGSSTGIFCG VMNNDWGELQ SADYKSLPQY LATGAARSII ANRISYFFDW HGPSVVVDTA
CSSSMVALHH AVTALQQNEC TLALATGTNL IQAPNIFIST TKIQMLSPTG RSRMWDANAD
GYARGEGVIS IVLKRLSDAI RDGDDIECVI RATGTNQDGR TMGLTMPSSV SQLQLIQSTY
ARAGLDPRRV QDRCQYFEAH GTGTLAGDPQ EAAAIHHAFF GPPASPEKNG VYNGCDVSVN
GAANGAFADD NDILLVGSVK TVVGHTEGTA GLAGIIKASL NLQHGLISPN LLFETLNPAL
EPFASHLKVV TELTPWPSLP TGAPRRVSVN SFGFGGTNAH AILESYDANV KESGSTVAAG
QSLTAALLPF VFSAASEGSL AAVLNSYAGY LKGKPALNLV DFAVTLLRRR SALKFRVSLW
ASSTEELIGK MEEEAEAIGK RTKTTNSRRC SDTPRILGVF TGQGAQWTQM GWELVGASPV
ARAWLEEMQN SLNDLPTKYR PSFSLTGELS NSVSKMKSAT LSQPLCTALQ IIIVNFLRAI
GVSFTSVIGH SSGEIAAAYA AGYLTATDAI RIAYLRGFMA SRAGGRNSQP GAMLAAGVSA
QEAADICAKS KGTITVAAEN APFSVTFSGD ANAIQSLEKK LKDENKFCRI LQVDTAYHSH
HMEPCCRPYL DALEECNISV KDAISGITWY SSVHPGDYID SASLRGAYWI ENMAMPVLFS
QAVAHALDEG DSPPDFVIEV GPHPALKGPV QQNIAEFFPA ASNVTYLAPC IRGSSSIASL
SNVIGSLWET IGAGAIDTTR YLRLFGLGQA KFIKDFPTYP FDHSRSYLAQ SRMIKNHLHK
RSVPHPLLGS LEPESADGEW RWRHYIRQKD LDWLNGHCIQ AQPVFPATGY IVMALEAASS
LSSRSIQSIQ LGDVAIHQAI TLPENEAEGV ETLFRFNRME TTDEMTSGTF HIHASTGDAF
QLRASGQMII SWGAPNPDLL AQSSGSGSAG MSAVDVDELY AFLAKVGYGY SGVFRGIRSL
YRQKDASHGE IQDVLPDGKP CRFLLHPALL DCTLQTMLGA IGAPDDGELY TLLVPTRIKS
VIVNSALCRN PTGETFLSNA NVTQIDADGI SGDVSLFTHN NEGIVQMEGV EIAPLVQPPT
ERVVFSKLAW GPLNPGHGSF ADPVDFSTHA LTMEHVALLY IKLVNSQLTD DERRNLAQDH
HRSRLAAWID RTLTKTSAGE HPILHKDWMN GTQADLDTLL AEASGSVMAE IANVVGTTLR
RFFRGEASIL EEVRKNDVLT RFYRHDVETE MMNERLGRIV GQLAFRYPRM KILEIGAGTG
SATHSILENI GRSYHSYTFT DISVGFFEEA RSAFAAHEDR FLFAPLNVEI DPAHQNFEAH
SYDLIVAANC LHATRSMVET MAHVRSLLKP GGYLVMLEIT NLDAIRATFL MGGFEGWWAG
EKDGRIWGPM LDVLTWEQLL RDSGFGGIDL RVGLGDPKLC LYEVLVAQAV NDQVNLLREP
LSAQAETHTQ QQWGDLLILG GSTAKTSALV KELGQMLKAR FHLVLVAPTL ESLSLTGCSQ
LSVLCLTDMD SPCFRGLTEQ RLQALQMLIS VTHKLLWVTA GPESDCLDLG LTKGWLRSLA
YERRESLHQY LNVENADAVT AELLATTLMR LVYTESGNDY MLSRLVHATE HEMYFRNGRM
DICRLQYEND MNQRYLSARQ WLSKQVRATD EISVVPVGKN RYKLRVGTGE RQLLRCQSVD
GVRIHVQYST VSAVPVGDGF LHLVLGEDKS TGARLIALTE RYENTIECPE SWTFKVRHEI
LAGKEALFLG ILAGVLLAAY LVDKTPPHST LFVHKAGPAL CNAIWTRALG KNVNPFFTTD
TPTSKTQNTT FVHPRVSTRR LKELLPRNIA VAAALDGNTT DGVSSRVKGL LSLPVRVETL
ETLYRSSPLR PVCGDTEIHD LLQSSCLLAT RLSDMDQQVT VVGIDTVANQ DVQPDHILNW
NPSSPFEAQV KPVTSLVTLS ASKTYILAGM TGDLGQSICE WMVSKGARHV VLASRTPKVA
PDWIRTMARK SARVLSLPMQ VLRIVSSMRT VLIVYRTIQQ QQFPAVGGVV NGALVLEDRL
FEQMTLDVMQ STFAAKVQGS MLLDELSGPD VDLDFFILFG SITGVVGNFK QTAYSAATGF
QSSLIHARRA RGLVGSIIHP GLISGVGYIT RKGSRWVQHV RKTTGSLLLS ERDIDKLFAE
AILAGRPECD SDPEIVIGLP LIDLEQHPDI FWSSNPLTWD FIDYSIKSTS QLGGTLHSRG
SLKAVLQSDS ISSIEDITPI VSEALIAKVR SKFSVSANTI VSPSTQLTDL GVDSLVAVDI
RTWFATELAV DIPLLQILGG ASIEELTATA VAKLPAGVDL IDDDSVLGTV
