ALNA_EMENI
ID ALNA_EMENI Reviewed; 2458 AA.
AC C8VJR7;
DT 05-DEC-2018, integrated into UniProtKB/Swiss-Prot.
DT 03-NOV-2009, sequence version 1.
DT 25-MAY-2022, entry version 87.
DE RecName: Full=Highly reducing polyketide synthase alnA {ECO:0000303|PubMed:30339758};
DE EC=2.3.1.- {ECO:0000305|PubMed:30339758};
DE AltName: Full=Asperlin biosynthesis cluster protein A {ECO:0000303|PubMed:30339758};
GN Name=alnA {ECO:0000303|PubMed:30339758}; ORFNames=ANIA_11191;
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 BIOTECHNOLOGY.
RX PubMed=21762468; DOI=10.1111/j.1755-148x.2011.00887.x;
RA Flori E., Mastrofrancesco A., Kovacs D., Ramot Y., Briganti S., Bellei B.,
RA Paus R., Picardo M.;
RT "2,4,6-Octatrienoic acid is a novel promoter of melanogenesis and
RT antioxidant defence in normal human melanocytes via PPAR-gamma
RT activation.";
RL Pigment Cell Melanoma Res. 24:618-630(2011).
RN [4]
RP IDENTIFICATION, DISRUPTION PHENOTYPE, FUNCTION, DOMAIN, INDUCTION, AND
RP PATHWAY.
RX PubMed=30339758; DOI=10.1021/acschembio.8b00679;
RA Grau M.F., Entwistle R., Chiang Y.M., Ahuja M., Oakley C.E., Akashi T.,
RA Wang C.C.C., Todd R.B., Oakley B.R.;
RT "Hybrid transcription factor engineering activates the silent secondary
RT metabolite gene cluster for (+)-asperlin in Aspergillus nidulans.";
RL ACS Chem. Biol. 13:3193-3205(2018).
CC -!- FUNCTION: Highly reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of asperlin, a polyketide showing anti-
CC inflammatory, antitumor and antibiotic activities (PubMed:30339758).
CC The first step of the asperlin biosynthesis is the production of the
CC intermediate 2,4,6-octatrienoic acid by the highly redusing polyketide
CC synthase alnA with cleavage of the PKS product by the esterase alnB
CC (PubMed:30339758). 2,4,6-octatrienoic acid is further converted to
CC asperlin via several steps involving the remaining enzymes from the
CC cluster (PubMed:30339758). {ECO:0000269|PubMed:30339758}.
CC -!- PATHWAY: Polyketide biosynthesis. {ECO:0000269|PubMed:30339758}.
CC -!- INDUCTION: Expression is controlled by the asperlin biosynthesis
CC cluster-specific transcription factor alnR.
CC {ECO:0000269|PubMed:30339758}.
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; an enoylreductase (ER)
CC domain that reduces enoyl groups to alkyl groups; a ketoreductase (KR)
CC domain that catalyzes beta-ketoreduction steps; and an acyl-carrier
CC protein (ACP) that serves as the tether of the growing and completed
CC polyketide via its phosphopantetheinyl arm.
CC {ECO:0000305|PubMed:30339758}.
CC -!- DISRUPTION PHENOTYPE: Fully eliminates the production of asperlin.
CC {ECO:0000269|PubMed:30339758}.
CC -!- BIOTECHNOLOGY: 2,4,6-octatrienoic acid is a particularly interesting
CC compound because of its potential as a natural tanning agent for human
CC skin. It is a promoter of melanogenesis and antioxidant defense in
CC melanocytes in vitro and in vivo, topically and systemically.
CC Pigmentation is a powerful protectant from UV damage and skin cancer,
CC and octatrienoic acid is an attractive natural photoprotectant.
CC {ECO:0000269|PubMed:21762468}.
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DR EMBL; BN001306; CBF82304.1; -; Genomic_DNA.
DR AlphaFoldDB; C8VJR7; -.
DR SMR; C8VJR7; -.
DR STRING; 162425.CADANIAP00009378; -.
DR EnsemblFungi; CBF82304; CBF82304; ANIA_11191.
DR VEuPathDB; FungiDB:AN11191; -.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_31_0_1; -.
DR InParanoid; C8VJR7; -.
DR OMA; EASAWHH; -.
DR OrthoDB; 19161at2759; -.
DR Proteomes; UP000000560; Chromosome VI.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0004312; F:fatty acid synthase activity; IBA:GO_Central.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IBA:GO_Central.
DR GO; GO:0019748; P:secondary metabolic process; NAS:AspGD.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IBA:GO_Central.
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 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; IPR011032; GroES-like_sf.
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; 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; IPR020843; PKS_ER.
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; 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; 1.
DR Pfam; PF08659; KR; 1.
DR Pfam; PF14765; PS-DH; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00826; PKS_DH; 1.
DR SMART; SM00829; PKS_ER; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF50129; SSF50129; 1.
DR SUPFAM; SSF51735; SSF51735; 2.
DR SUPFAM; SSF52151; SSF52151; 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 Multifunctional enzyme; Oxidoreductase; Phosphopantetheine; Phosphoprotein;
KW Reference proteome; Transferase.
FT CHAIN 1..2458
FT /note="Highly reducing polyketide synthase alnA"
FT /id="PRO_0000445939"
FT DOMAIN 2359..2441
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:30339758"
FT REGION 51..476
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30339758"
FT REGION 488..515
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 609..932
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30339758"
FT REGION 1001..1305
FT /note="Dehydratase (DH) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30339758"
FT REGION 1740..2051
FT /note="Enoylreductase (ER) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30339758"
FT REGION 2076..2264
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:30339758"
FT ACT_SITE 221
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 221
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 697
FT /note="For malonyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 1032
FT /note="For beta-hydroxyacyl dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2401
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2458 AA; 267558 MW; C528BF4C4C23EBC4 CRC64;
MNLPGEIHHR FTYMYIAQVS FADLDITKHN LPISTMSSSD SPNYGDATMP IAIVGMAARF
SGEATNPSKL WDMMVQGRTG HSAVPENRFD AEAWHHPSHE RRGTIQPRSG FFLREDPAVF
DAPFFSMTAK EAAGMDPMQR KLLEISYEAF ENAGIPITKL PGTATGVYSG VMTNDYELMT
AGDPMQLPQN AASGTSRAML ANRISWFYDL RGPSFALDTA CSSSLYALHL ACQSLQAGET
DQALVTGVNL ILAPNFISQL SSMHMLSPDG KSHSFDSRAN GYARGEALAA VVVKPLYQAL
ADGDTIRAVI RGSGANQDGK TVGITIPNPQ AQAELIRKTY ATAGLGLEQT GYFEAHGTGT
PVGDPIELSA IGTSFGEHRS QNCPLFVGSV KTNVGHTEGA AGLAGVVKTV LALEAGIIPP
LADFQELNEK LRLEEWKLAL PLKATPWPMP GLRRASVNSF GFGGANAHVI LDDAYHYLKS
HGLSANHHTT LSESEDSSDS GLEMDSSTSD SGEGQSSKLL LFSAYDGAGI KRTEASWNSH
LADILADSKT VDETMGMNDL AYTLSDRRTT FDFRSFAVAS SVQDLKAKLE NDGLPRLNRA
SRRSNPVFVF TGQGAQWPAM GRELLSNPIF RASIERSKAV LELEGCEWDV VQVLSDPQDQ
RIHIPAFSQP VCTILQVALV DLLQSWGIQP AATVGHSSGE VAAAYAAKMI SQDEAVRIGY
WRGFYSEQVK ARLENIRGSM MAVGLSESQA TSYLNRVPEG SVVVACINSP SSVTLSGEDH
SIKTLEAILQ ADGHFARKLR VEVAYHSPHM KTVADEFLNA VGIITPQPSE IPMFSSVTET
RVEDPATLVA SYWMQNLISP VRFSGALATL LNDTPSVKAN TRRRRTAGIV WSALIEVGPH
EALKGPCRQI MSGLNTKLAD QIPYMSVLSR GKSAVETSLT AAGLLWASGH PINIREVNQY
RDTGERVITD LPPYPWNHEK GFWHEPAASI SARLRKEPRN DLLGVPVAQQ NPFERCWQNY
LSVSECPWQK DHVITGTVLY PGAGHLIMAF EAAIRLAADN RPLKGVSFSD VHFDKGLVIP
SDDHGVETRL CTRPHESLLD WYHYTLYSIN ATGDWTKHSW GSFSLHYEDA VSVQQAKRSK
GEYDDINTRA CRKLDVESFY EQLLSIGTEY GPTFRNLVHA AAAPGYHSGV GTITIPDTKS
VMPHEFEYPH LIHPATLDAI FHLIFVAMGE GNALSESAIP TRVDRIYIST DLPRGVGAKY
TGYGRAEPVS SRDTLGTIVV SDENWSAGPK IIVEGMTVTE VSAGASTSFN SLLIPGGQGR
IATLEWKEDV DSLVGPTAES WLAQKGPSIG GQASDVTEAV QRLDAWLELS CFKSTDLGTL
VICPSKLKGS FELVKKYGSK HGERYRFGRT TIIEFSENDI SAAESAFAPH GIESSYAAID
LSATPEHAME QLGMFDLIIA EENVIVQFPD VTKILHREGR VAIIRSHALP DERHFAATKG
LLKEISFESQ DGSILQIAGL GLEMDPAIRS LDDVVLLQHV DASPAAKNFE KRLTAQLTSL
GAHVRSNTIA NASSLSGNIV ISLLEIDCQF VISWTSEEFE QFRQLTNARY VLWITRGGLL
DADRASLDYA PSTGLLRTVR VEKPQIRLPH LDLSPSLDLN SDRAVEIVIS AFHSSIKPSV
KEKNLEMEYA ESNGLLYIPR ARGHAALDHE LALRGEKVSS IPGPLSAPGI ARRLETSLAG
SPSQARWVPD ETVGDKLADF DVEIQVSHVG LEHSKVENYL NGKQLSLAPG LGRVAVGTLT
RAGAKVSRFI PGDQVFALHA APFHTHLRVT EDAVHAVPDI LSPAQAAHLP LAAARAWHSL
IDVAAFRAGQ SVFVNGASDT VGRLTVELAR LLKGDVFASV SSDDEKHTLT KTYNIPEDHI
FSLSHRTDWA SDLKAAMGQG QLDIVINNAT PSPAIRSLFQ SIAPKGRFVD LTQRLDPSLL
DPRMFQRNVT LSLVDWESLT NPQLGALMVR SLDLLRAGAL TPIKEEYIFS VSDLPEALLS
VGQQQHERVA APVVVEFSAD ATVPLLPSLP APLHLKPDAT YILAGGLGAL GLTIAENMCS
HGAGHLVFLS RSGASSQRQQ EALESFRARG CKVDVVKCDV TDQEQVQALA TQIREQSWNV
RGIIQLAMVL RDSIFENMTF DKWETAVNPK IKGTWNLHAE LPKDVDFFII LSSLSGIIGN
TAQANYCAGN TYEDALAHYR RKQGLAATTL NVGLVTDASH FNENSTIEDY LRKYSHWIAA
QVTDSELQHT ITAVMRRTVG DKNEPVPDQL LVGLSDNVRR DGNSLNLWPQ DRKFDHRISL
EDGLGVVEKD TNQQKLKAST TVAQAHEVVE TALRLNVAAA MTASPDDIDI EKPLYAFGID
SLKGIEVRNW IFSELQADVS VFEVLSPMTL SRLALKIVSK STLVGAELAA EAAADSVA
