TAZB_ASPTN
ID TAZB_ASPTN Reviewed; 2620 AA.
AC Q0CS88;
DT 03-AUG-2022, integrated into UniProtKB/Swiss-Prot.
DT 17-OCT-2006, sequence version 1.
DT 03-AUG-2022, entry version 106.
DE RecName: Full=Highly reducing polyketide synthase tazB {ECO:0000303|PubMed:35398258};
DE Short=HR-PKS azaB {ECO:0000303|PubMed:35398258};
DE EC=2.3.1.- {ECO:0000305|PubMed:35398258};
DE AltName: Full=Azaphilone biosynthesis cluster protein B {ECO:0000303|PubMed:35398258};
GN Name=tazB {ECO:0000303|PubMed:35398258}; ORFNames=ATEG_03446;
OS Aspergillus terreus (strain NIH 2624 / FGSC A1156).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=341663;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=NIH 2624 / FGSC A1156;
RA Birren B.W., Lander E.S., Galagan J.E., Nusbaum C., Devon K., Henn M.,
RA Ma L.-J., Jaffe D.B., Butler J., Alvarez P., Gnerre S., Grabherr M.,
RA Kleber M., Mauceli E.W., Brockman W., Rounsley S., Young S.K., LaButti K.,
RA Pushparaj V., DeCaprio D., Crawford M., Koehrsen M., Engels R.,
RA Montgomery P., Pearson M., Howarth C., Larson L., Luoma S., White J.,
RA Alvarado L., Kodira C.D., Zeng Q., Oleary S., Yandava C., Denning D.W.,
RA Nierman W.C., Milne T., Madden K.;
RT "Annotation of the Aspergillus terreus NIH2624 genome.";
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP FUNCTION, INDUCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=35398258; DOI=10.1016/j.fgb.2022.103694;
RA Sun W.W., Li C.Y., Chiang Y.M., Lin T.S., Warren S., Chang F.R.,
RA Wang C.C.C.;
RT "Characterization of a silent azaphilone biosynthesis gene cluster in
RT Aspergillus terreus NIH 2624.";
RL Fungal Genet. Biol. 160:103694-103694(2022).
CC -!- FUNCTION: Highly reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of azaterrilone A and other azaphilones,
CC a class of fungal metabolites characterized by a highly oxygenated
CC pyrano-quinone bicyclic core and exhibiting a broad range of
CC bioactivities (PubMed:35398258). The first step of the pathway begins
CC with the non-reducing polyketide synthase tazA that assembles one
CC acetyl-CoA starter unit, five malonyl-CoA units, and catalyzes a series
CC of Claisen condensations, methylation, PT-mediated cyclization, and
CC finally releases the first hexaketide precursor through the R-domain.
CC The tazA product then undergoes reduction on its terminal ketone and
CC the following pyran-ring formation by yet undetermined enzyme(s).
CC Dehydration and enoyl reduction, possibly involving the trans-enoyl
CC reductase tazE leads to the next intermediate. TazD is predicted as an
CC acetyltransferase and might catalyze the acetylation steps leading to
CC the synthesis of azaterrilone A. Azaterrilone A is not the final
CC product of the taz pathway and both the highly reducing polyketide
CC synthase tazB and the dual enzyme tazHJ catalyze late steps of the
CC pathway, leading to the production of the 2 final stereoisomers that
CC contain additional polyketide modification whose structures have still
CC to be determined (Probable). {ECO:0000269|PubMed:35398258,
CC ECO:0000305|PubMed:35398258}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:35398258}.
CC -!- INDUCTION: Expression is positively regulated by the azaterrilone A
CC cluster-specific transcription factor tazR.
CC {ECO:0000269|PubMed:35398258}.
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:35398258}.
CC -!- DISRUPTION PHENOTYPE: Does not affect the production of azaterrilone A
CC but impairs the production of the 2 final isomers.
CC {ECO:0000269|PubMed:35398258}.
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DR EMBL; CH476597; EAU36720.1; -; Genomic_DNA.
DR RefSeq; XP_001212624.1; XM_001212624.1.
DR STRING; 33178.CADATEAP00006812; -.
DR EnsemblFungi; EAU36720; EAU36720; ATEG_03446.
DR GeneID; 4317679; -.
DR VEuPathDB; FungiDB:ATEG_03446; -.
DR eggNOG; KOG1202; Eukaryota.
DR HOGENOM; CLU_000022_31_0_1; -.
DR OMA; LVAMEFR; -.
DR OrthoDB; 19161at2759; -.
DR Proteomes; UP000007963; Unassembled WGS sequence.
DR GO; GO:0016746; F:acyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0016491; F:oxidoreductase activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0071704; P:organic substance metabolic process; IEA:UniProt.
DR GO; GO:0044550; P:secondary metabolite biosynthetic process; IEA:UniProt.
DR GO; GO:0044281; P:small molecule metabolic process; IEA:UniProt.
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; IPR002328; ADH_Zn_CS.
DR InterPro; IPR011032; GroES-like_sf.
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; 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; IPR009081; PP-bd_ACP.
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; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF08659; KR; 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 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; PS00059; ADH_ZINC; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 2: Evidence at transcript level;
KW Acyltransferase; Metal-binding; Multifunctional enzyme; NADP;
KW Oxidoreductase; Phosphopantetheine; Phosphoprotein; Reference proteome;
KW Transferase; Zinc.
FT CHAIN 1..2620
FT /note="Highly reducing polyketide synthase tazB"
FT /id="PRO_0000456065"
FT DOMAIN 2539..2620
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 26..419
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 601..923
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 993..1313
FT /note="Dehydrogenase (DH) domain"
FT /evidence="ECO:0000255"
FT REGION 1379..1680
FT /note="Methyltransferase (CMet) domain"
FT /evidence="ECO:0000255"
FT REGION 1910..2227
FT /note="Enoyl reductase (ER) domain"
FT /evidence="ECO:0000255"
FT REGION 2251..2425
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255"
FT ACT_SITE 166
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2576
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2620 AA; 287510 MW; B9E3139B43D3A125 CRC64;
MPFLNGNTTH HEAHSAEPDH GNTEPMVIIG LAMRAADEAT DAEAFWDFLF YVKGAAFLEE
SPNGFDAAFF KMSKTEVQSL DPQQRILMEN VYHALENAGL PMEDVISSNT SVFVSGFNYH
HADRLNSDLE LSFKHRPTGA ENSMISGRVS WFYDFQGASL TIDTACSSSL VGLHLARQSL
QAKESDMAIV SGVSVIGYLS HLMKMSYSGL LGSEGKSLAF DQRADGYGLG EGVGTVILKT
LSAAIRDGDT IRAVVRGTGL NHDGHTPGMT YPSAAAQESL IRKTYVAAGL DPKDTIYAES
HGTGTQAGDL MECTAIAAAF ETEKRDRPFY IGAVKPNVGH LEGGAGITSV IKSVLLLESG
IIPPNATLKK INPKIRPEWN LQFPTRCVPW PTTGIRRSSI SSYGISGTNA HCILDDAYHY
CNQRGISVRH RTAETVPSEK EIELIVAKAV RRYQTNSANG FNKFDEPRGS DSAGSNANGS
HGVAGTVGAN GNGVNGINPS PGHMPENTKA LQASSLLLFS AFDEKSLEKV LAQIRNYISS
LDSNSAGQAL HDLAFTLSTR RSRLPWKTYA LCSSLVELHD MLSKPHLKAI KSRSPLRVGF
VFTGQGAQYA QMGQQLLLYP VFRQSLEEAS LYFKSLGCDW SLLEELTRDS KDSRISKSAF
AHPLSCAVQI ALLDLLLSWN VVPHRVVGHS SGEIAAAYCA GKISREGAWR VAYYRGHVLL
HGKTDRVGGM LAAGIEEEPL LDLLSQVHAA LPGGTLSIAC YNSPRNHTIS GDDAMVDALK
VLLDEQGIFT RKLKVEHAAH SAHMEQFTGE YEELVGDLPS NRLLHFDHTV HMFSTLTGRL
IDDSCVPEKS SHWSNSMVGP VEFTKAVSSM CFDSILGDGS SVQGSQVDVI LEVGPHPAMQ
SAVKDILGLG SGIPYLATLS RKDTGLGTLL DTIGSLAAHG APVDLDKVNR SANPLLKPRM
LADLPPYPFS HEEQGLYESR LIKNIRLRQF PRHDLFGAPV PDWNPNSPRW RHFLRVSENP
WLKEHVIGDE FVFPGAGYMV MAVEGMKQIT DPAEMVGIFL RDVKFKAMLV VPDDTQGVEV
CLSFYPVPES RTSLSTAWKR FEVASYNQKT EEWIEHCTGE VSPDLKKSLN PIDGTRTQEA
EKAQFSAFAQ SRQDVCTAPV DFTPVYDHLR KIGVNHGPSF RNLAAVNIGD REQGLMTGDI
VVPDITQVMP EKYAHGHLIH PTTLDNAFHA SFASIYDLEG KTMMRRGCVP SYVQDVWLSA
TALSSDPGTI LRCTSEASHA LHGAFESTVH AWDPANPSER LISLAGIRLS PFKPESSESI
AAENRTCYSV EWYPDLNLLT KREFQKLLSR FPAPLETFDA QQKWFSQLQL ASTLLATDGL
RESREMKDVN LEDHQRGYRE LLRAIAAGVT TQSIPYVSLD MWLEYSRNSD LKEQLYREIE
DQSPDGALLV RMGAAIPSIL GREITAQYLL YEQDDLLSVW DENRLSRGKI LPALTQYLTL
LRKSQRGLRV LELGSRTGVL AEHVLKTLCV DGTENSIEQY TIRSQSADHC EKLKKRLSAW
VDIIRYEALD LTAKSSEQEI QINPFDLVIV NNFVRGQPNM EEMMLRLNSL MRQGGRLLIL
EDVRSESLHA NIIFGALPGW REATKASWDA ESGTDKLEWD RVLRNTGFSG VDFEASSSIY
PDFADFSLVA STASHGMLEA TPPSFEVLVI IQSHSEISRS LARGLLTAGV SHSICLIDDI
RADNVIGRVC ISLLEAEQPI LNSMDETTFQ AIQNLVTACD SLLWVTGDPL AHPEFQMATG
LIRTIRWELD RNDLNLITIA LDGESTASTD MNVDALIRVL RYQFLDQCSK DSGNTNSEYR
IRDSVIETNH AVKNTVASAV IEAQFSSPKP TLSTWESIER PVRLINTSPG IDSLTWVTDE
DISRKPLAVN EIEIDVHAVG LNFKDLLVAM GEIDQPGFGH EAAGIVVRVG SSVSTFKAGD
RVMYLGDPSP GKMGTLRTRS RVHCGLAIKI PDTMGFEIAA GLPIIYGTVI YSLGHIARLR
AGEKVLIHAA AGGIGQAAIQ YAHAKGAEIF VTLSSLEKKQ YIMENFHIRP DHIFSSRDLN
FAAGIKRIAP AGVDVVLNSL SGEALRQSWQ CVAPFGRFVE IGKLDLQAGS KLDMTPFLYN
VSFSGVDLNA LAENRPEVCQ ELLQETIDLW SNQDIHEARP TQVLDYGQLK EGLRLLQTGK
SIGKVTLVPG THPVSVIPPP FLPLELDANA SFILAGGLGG IGRSIALRLA RRGAKHIVFL
SRSATVHEAG QETIAKLKLL GCTSHVFQCD ISNETRLLEV ITRVRETLPP IKGCIQCSFV
LKDKAFDSMT HEEWQTALTP KVSGSWNLHC LLPDVDFFLL LSSITGIVGN RSQANYNAGN
NFQDSLARYR VSKGMHGASV NLGAVVGIGF IAENAEYAAK HTFKMANPQT EEEVLATVEY
LIDRRHHMAL SPDTAQLICG LRTPASYSLS NEAPPTHLKY PMFAQLPPAL SNTGPGGSHS
AQSATHIRDQ LQSATAPEEA ARIIHKALRR KMADLLNISE DTIDDSLNVR ANGVDSLIEM
EFRTWFAKEL GATVPLKDLA KDLTQLSARL VSLSSFTKFR
