VALA_ASPTE
ID VALA_ASPTE Reviewed; 2521 AA.
AC P9WEV0;
DT 12-AUG-2020, integrated into UniProtKB/Swiss-Prot.
DT 12-AUG-2020, sequence version 1.
DT 03-AUG-2022, entry version 8.
DE RecName: Full=Highly reducing polyketide synthase valA {ECO:0000303|PubMed:28604695};
DE Short=HR-PKS valA {ECO:0000303|PubMed:28604695};
DE EC=2.3.1.- {ECO:0000305|PubMed:28604695};
DE AltName: Full=Valactamide biosynthesis cluster protein A {ECO:0000303|PubMed:28604695};
GN Name=valA {ECO:0000303|PubMed:28604695};
OS Aspergillus terreus.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=33178;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, DOMAIN, DISRUPTION PHENOTYPE,
RP AND PATHWAY.
RC STRAIN=ATCC 20542 / MF4845;
RX PubMed=28604695; DOI=10.1038/nchembio.2408;
RA Clevenger K.D., Bok J.W., Ye R., Miley G.P., Verdan M.H., Velk T., Chen C.,
RA Yang K., Robey M.T., Gao P., Lamprecht M., Thomas P.M., Islam M.N.,
RA Palmer J.M., Wu C.C., Keller N.P., Kelleher N.L.;
RT "A scalable platform to identify fungal secondary metabolites and their
RT gene clusters.";
RL Nat. Chem. Biol. 13:895-901(2017).
CC -!- FUNCTION: Highly reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of valactamides (PubMed:28604695). The
CC first step of the pathway is performed by the highly reducing
CC polyketide synthase valA that produces the polyketide part of the final
CC products (Probable). An acetyl starter unit is incorporated by the
CC ketosynthase domain of valA, and subsequently 6 malonyl-CoA-derived
CC ketide units are incorporated and fully reduced to their respective
CC alkane forms by the action of the ketoreductase, dehydratase, and
CC enoylreductase domains (except for the penultimate unit, which is
CC reduced only to the alkene) (Probable). The final five ketide units are
CC each proposed to be alpha-methylated by the methyltransferase domain
CC before ketone reduction by the ketoreductase domain (Probable). The C1
CC domain of the nonribisomal peptide synthetase valB then catalyzes amide
CC bond formation between the heptaketide chain and L-valine (L-Val)
CC attached to the T1 domain (Probable). The C2 domain incorporating L-
CC isoleucine (L-Ile) then carries out chain elongation, which is followed
CC by macrolactonization by the Ct domain to release the final product
CC (Probable). {ECO:0000269|PubMed:28604695, ECO:0000305|PubMed:28604695}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:28604695}.
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; an
CC enoylreductase (ER) domain that reduces enoyl groups to alkyl group; 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:28604695}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of valactamides A-H.
CC {ECO:0000269|PubMed:28604695}.
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DR EMBL; KX449366; AQM58285.1; -; Genomic_DNA.
DR AlphaFoldDB; P9WEV0; -.
DR SMR; P9WEV0; -.
DR VEuPathDB; FungiDB:ATEG_03574; -.
DR VEuPathDB; FungiDB:ATEG_03575; -.
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: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; 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; IPR013149; ADH-like_C.
DR InterPro; IPR013154; ADH_N.
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; 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; 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; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF08240; ADH_N; 1.
DR Pfam; PF00107; ADH_zinc_N; 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; PF00550; PP-binding; 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; 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 3: Inferred from homology;
KW Acyltransferase; Methyltransferase; Multifunctional enzyme; NADP;
KW Oxidoreductase; Phosphopantetheine; Phosphoprotein;
KW S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..2521
FT /note="Highly reducing polyketide synthase valA"
FT /id="PRO_0000450619"
FT DOMAIN 2444..2521
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:28604695"
FT REGION 9..436
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28604695"
FT REGION 435..454
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 558..883
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28604695"
FT REGION 951..1263
FT /note="Dehydrogenase (DH) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28604695"
FT REGION 1413..1610
FT /note="Methyltransferase (CMet) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28604695"
FT REGION 1833..2146
FT /note="Enoylreductase (ER) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28604695"
FT REGION 2172..2348
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:28604695"
FT ACT_SITE 177
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 648
FT /note="For malonyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 982
FT /note="For beta-hydroxyacyl dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2481
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2521 AA; 275484 MW; CB17C1804281EDFD CRC64;
MSLPAQSPIA VVGVAYRAPG IGRKGLYEFL AEGKSAFSPV PKERFEQGAY HHRNSEKAGV
FSPEGAHFLP DDIYAFDAPF FNLNADEVRS MDPQHRMLLE CAFEAAESAG ITLAKLHGTK
TGVFASLERC GYGEELLNDL PTSTKYTVFS TAGCMAANRL SYFFGLEGPS ISLDSACSSS
VYALHLACQS LRMAECSAAF VGAATLIINA KPIIALDTMG ALSPDGKSYA YDSRRNGFGM
GEGGGCLILK RLEDALEAGD PIQAVIRHTV CNHSGRTRGI TMPSQLAQED LLLRVHTEVG
LKTGDTSVVE GHGTGTQVGD PIETRAIANI IAKDRADPVY IGSVKSNLGH LLSSSGMLAI
VKAICMLQHA TIFPNSGFKE MSPEIDALKL RVAKTCLPWQ ARGPRRVCTT NFGFGGSNAA
VLLEEFQDKS LITGPGNGNK ISHGPSRPPL QTKDGIDANG QSSKSYQRLF LLSAKSEKSL
TRLLSSFALH LTKVPTSVAG DRYLADLSFT LNQRRTHFSH RIALVADSVE DLTQQLSTRS
ENRTGKAYPG QEVVPLFVFT GQGAQHSRMA AELDQYKPFA MAILRAERYL QEFGATWSLT
KELFQCDGEK SRINEAEISQ PACTAIQLGL VLLLRSWGIS PAIAVGHSSG EIAAGYAAGA
LSFKTAMAIA FFRGKSTMEC RRKNRSGLGG MVALGTDVET ATRLVESTAR VGRASIAAIN
SPSSVTISGD IAAVNRIAQI ADVQGIFNRK LKLDVAYHSH HMEPATASYQ AAIEPYCAAE
RTRSKSNGII TTDRASFFSS VTGCTESADV IQSASYWTEN LVRPVKFSQA MQNILSQLGS
DKRTVAAIIE LGPHAALKGP INQILQSNIE IQSAYLPTLL RDYKNTETLL GLAGRMFTMG
SSLNLAAVNN TTSKDARVLT DLPSYEWSKE TRYIHEYPRS VQEKHPGHHY NPLLGWKIPS
EGNDHIFRQV FTLDEMPWIR DHEVAGDAVF PFVGFVRQAV EAFKAIPKTT SEVSSVSLRE
LHIKRSLRVD NAGRVDMITK LRPAETGMGA FSSTIWVFEI MTWTESAGWT VHAHGRIGSE
AVDFAAGGGP ERTMAEEVLS MAQPTATDAE REYKILQESG ISFGPRFRNM IALWAAPGIA
VHETQPPRTD EDSFQGSHTF LELVTLDSML HSAGIAIGQD DNNGGIRPVY VPVCSSRLQL
STIPVTAEHR FITVTRRLER DRKSGTSRIN FVVFVITQSG RVPYLELDMT LQRITQLNNI
VNLSREELPE GFYDTLVPHI GFADGKMLAR HFADNNLVAS GRHMRHQLAN VSLHFLACAL
KTTTDVNRAM IPFHHQKFLH WAKELVADAV IPQVTPQLIE EVSKCSAVGE LLRAVGEQIP
QILRGQVQPL ELMMKDGLLT RSYEDSITLH TCNKALAAYV SGLGEINPEL RILEVGAGTG
SATLPILEAL SGGEATDNDS VPNFSSYHYT DISTGFFENA RRKLSRWPQL TYQKLDIRHH
PAEQGFKVGS YDLVIAVNVL HATPDLKATV QHVRALLKPG TGKLGIVEHT DNNDPTVLPF
ALLPDWWSVS DEFRQSRGGP LMSREHWNRL LVSAGFSGVE GAVESGEDSL FWTSMVEEHT
DFLSDALDEV TIYGSLTDPS EIKLAESVAR AMSGIPHLPI PRVKPLAELD DVQGSYSILL
DNPQRSVLST ISSEDEFNKL KSVLLSSKGL LWVSPENRCP EYARIKGILR TLRLEESARK
FLHVDGIPLD SIRGASAVAH LALALVRDKA PAAFREQEFV WHNDMLHVPR LRKLQEARET
FALESGISIC KEQPIWQSHG PENVLRLSIE TPGDLDSIYF ERHSLSRTAL CDDEILIQVS
AVGINFRDVL ALLGRIPWSP PGREGTGTVM QVGANVSHLQ AGDRVFFMVL EGALGTYVRT
PGQFARKVPQ SISTADAAGL VAAYVTALVC LDHVARIRQG ESVLIHAASG AVGQACILLA
QTRGADVFVT AGSAEKRQFL HETFEIPESH ISSSRTLEFR HRVLKQTGGK GVDVVVNCLS
GQLLQETWSM VTDFGRFVEI GKKDILENSH LSMGKFSCNV TFAAVDLTQY FHQRPEVLHS
CLDEIVDMLE AKAIWPIQPV TPIPISDIQS GLRRLQSGHN IGKIVAILGP DERVKAERQS
PLQKEKPLQA DATYLITGGT GGIGRSLVPM LLDNGAANIV LLGRSGDSSR DVKRLIQQYS
RPQCGIQVRA IACDVVSRVS LSTALHAVKD LPPVRGVIHG SLYLRDSLFM NATFEDWRKI
SGPKIDAAWH IHELLPGLDF FVALSSGIGI VGNVGQSIYG GSSTFLDAFA QYRARQHLHS
VSISLPVIDD IGYVKEREGL RARLMEENVS FKLSIAQVLA AVKGAIIGRS SGLNKDSRAF
LFVREDSVAS QGWENRWHYL YPARRRNAAK VAGSGQDVDR STPSGEEGRL EALCNKVSSI
TMIDREDVTP SRSLSEYGLD SLVAVELRHW IRREFGADLA LTHIVGAESL QALSSRIVAQ
G
