CAZM_CHAGB
ID CAZM_CHAGB Reviewed; 2746 AA.
AC A0A0K0MCJ4;
DT 17-FEB-2016, integrated into UniProtKB/Swiss-Prot.
DT 11-NOV-2015, sequence version 1.
DT 03-AUG-2022, entry version 25.
DE RecName: Full=Iterative polyketide synthase CazM {ECO:0000303|PubMed:26172141};
DE EC=2.3.1.- {ECO:0000305|PubMed:26172141};
GN Name=cazM; ORFNames=CHGG_07645 {ECO:0000312|EMBL:AKA40070.1};
OS Chaetomium globosum (strain ATCC 6205 / CBS 148.51 / DSM 1962 / NBRC 6347 /
OS NRRL 1970) (Soil fungus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Sordariomycetidae; Sordariales; Chaetomiaceae; Chaetomium.
OX NCBI_TaxID=306901;
RN [1] {ECO:0000312|EMBL:AKA40070.1}
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], X-RAY CRYSTALLOGRAPHY (1.40
RP ANGSTROMS) OF 1-395 IN COMPLEX WITH HEXANOYL-COENZYME A, FUNCTION,
RP CATALYTIC ACTIVITY, ACTIVE SITE, COFACTOR, PATHWAY, DOMAIN, AND MUTAGENESIS
RP OF CYS-155 AND HIS-277.
RC STRAIN=CBS 148.51 {ECO:0000312|EMBL:AKA40070.1};
RX PubMed=26172141; DOI=10.1021/jacs.5b04520;
RA Winter J.M., Cascio D., Dietrich D., Sato M., Watanabe K., Sawaya M.R.,
RA Vederas J.C., Tang Y.;
RT "Biochemical and structural basis for controlling chemical modularity in
RT fungal polyketide biosynthesis.";
RL J. Am. Chem. Soc. 137:9885-9893(2015).
RN [2]
RP IDENTIFICATION, FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23072467; DOI=10.1021/ja3090498;
RA Winter J.M., Sato M., Sugimoto S., Chiou G., Garg N.K., Tang Y.,
RA Watanabe K.;
RT "Identification and characterization of the chaetoviridin and chaetomugilin
RT gene cluster in Chaetomium globosum reveal dual functions of an iterative
RT highly-reducing polyketide synthase.";
RL J. Am. Chem. Soc. 134:17900-17903(2012).
CC -!- FUNCTION: Polyketide synthase; part of the Caz gene cluster that
CC mediates the biosynthesis of the azaphilones chaetoviridin A and
CC chaetomugilin A (PubMed:26172141, PubMed:23072467). The substrate
CC (S,E)-4-methyl-hex-2-enoyltriketide is transferred from the CazF acyl
CC carrier protein domain to the CazM N-terminal acylcarrier protein (ACP)
CC transacylase domain, and from there to the phosphopantetheinyl group of
CC the CazM ACP domain, where it serves as a starter for the biosynthesis
CC of cazaldehyde A, the precursor of chaetoviridin A and chaetomugilin A.
CC During this process, CazM consumes malonyl-CoA, S-adenosyl-L-methionine
CC and NADPH to catalyze four rounds of chain elongation, cyclization and
CC ultimately NADPH-dependent product release (PubMed:26172141).
CC {ECO:0000269|PubMed:23072467, ECO:0000269|PubMed:26172141}.
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000305|PubMed:26172141};
CC Note=Binds 1 phosphopantetheine covalently. {ECO:0000255};
CC -!- PATHWAY: Polyketide biosynthesis. {ECO:0000305|PubMed:26172141}.
CC -!- DOMAIN: Multidomain protein; including an N-terminal starter unit:ACP
CC transacylase (SAT) domain, a beta-ketoacyl synthase (KS) domain, a
CC malonyl-CoA:ACP transacylase (MAT) domain, a product template domain, a
CC acyl carrier protein (ACP) domain, a methyltransferase domain and a
CC reductive NADPH-binding domain that is required for NADPH-dependent
CC product release. {ECO:0000305|PubMed:26172141}.
CC -!- DISRUPTION PHENOTYPE: Abolishes the production of azaphilones.
CC {ECO:0000269|PubMed:23072467}.
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DR EMBL; KP764718; AKA40069.1; -; Genomic_DNA.
DR EMBL; KP771866; AKA40070.1; -; mRNA.
DR PDB; 4RO5; X-ray; 1.60 A; A=1-395.
DR PDB; 4RPM; X-ray; 1.40 A; A=2-395.
DR PDBsum; 4RO5; -.
DR PDBsum; 4RPM; -.
DR SMR; A0A0K0MCJ4; -.
DR STRING; 38033.XP_001225301.1; -.
DR eggNOG; KOG1202; Eukaryota.
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 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; -; 2.
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; IPR013120; Far_NAD-bd.
DR InterPro; IPR041068; HTH_51.
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; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR042104; PKS_dehydratase_sf.
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; IPR032088; SAT.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF18558; HTH_51; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF08242; Methyltransf_12; 1.
DR Pfam; PF07993; NAD_binding_4; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF16073; SAT; 1.
DR SMART; SM00827; PKS_AT; 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 3D-structure; Acyltransferase; Multifunctional enzyme; NADP;
KW Phosphopantetheine; Phosphoprotein; S-adenosyl-L-methionine; Transferase.
FT CHAIN 1..2746
FT /note="Iterative polyketide synthase CazM"
FT /id="PRO_0000435431"
FT DOMAIN 1754..1828
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 1..395
FT /note="N-terminal acylcarrier protein transacylase domain"
FT /evidence="ECO:0000305|PubMed:26172141"
FT REGION 384..419
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 685..803
FT /note="Ketosynthase domain"
FT /evidence="ECO:0000255"
FT REGION 969..1260
FT /note="Acyltransferase domain"
FT /evidence="ECO:0000255"
FT REGION 1701..1754
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1833..1906
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2091..2283
FT /note="Methyltransferase domain"
FT /evidence="ECO:0000255"
FT REGION 2372..2618
FT /note="NADPH-binding domain"
FT /evidence="ECO:0000255"
FT COMPBIAS 403..418
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1701..1715
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1836..1854
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1855..1888
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 155
FT /note="Nucleophile; for transacylase activity"
FT /evidence="ECO:0000269|PubMed:26172141"
FT ACT_SITE 277
FT /note="Proton donor/acceptor; for transacylase activity"
FT /evidence="ECO:0000305|PubMed:26172141"
FT ACT_SITE 599
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 1788
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT MUTAGEN 155
FT /note="C->A,S: Abolishes enzyme activity."
FT /evidence="ECO:0000269|PubMed:26172141"
FT MUTAGEN 277
FT /note="H->A: Abolishes CazF-dependent enzyme activity, but
FT not activity with an in vitro substrate analog."
FT /evidence="ECO:0000269|PubMed:26172141"
SQ SEQUENCE 2746 AA; 298868 MW; BE5C84ABA6D8F125 CRC64;
MISVADLDYA SRKSSIFLFA PHVGTFTKQS MDKLVRPLAA SAHRDWILDT VAGLPTYWDA
LAVKIPNIGN AIPGRRQLTD LDTWFRHGAG DVTQDDATLP SIVVGPLVVL IQLTQYWRYL
ELTRPDHLED SADLQADVVT RQTQPGAKVE TLGFCAGLLA AVAVASAGNR QEFQKYGAVA
VRLAMMAGAL IDGQEARDKA TRDGGSVSYA IAWRGQKPGE EAARIVKDLN PNAYFAVLYD
EARATVTTTR RTAPSLVNRL RAADVTVAEI GIKGRIHSPD SERKNNTDLL VDLCKSFEDL
QYADAASLAL PTYNNEAEGR PVSRDRGNMT EMVIRAILVN QCNWYGTFKG ATEGREPFVV
TLGLERSVPP TLMRSLGPHQ VHYEDLADNG IPPAPQSPPR AVIETQPQPQ QQQDTTPPKI
LENDKDAIAV VGMSIKTAGA DDLDEFVEML KTGRSQHEPV TRERLMHDML FRAAADSDPN
HKYYGCFIRD SDAFDHRFFK RSPRESAAMD PQSRLAMQAA YQAVEQSGYF TETTAAPEGR
DKKHVGVYLG VCGMDYDHNS TCHEPSAFTA TGALRSFITG RVSHYFGWTG PSMTFDTACS
SSAVAIHTAC RNLLSGECTA ALAGGANTIT SMLWFQNLSA GSFVSPTGQC KPFDDAADGY
CRAEGMAFVF LKKLSDAVRD GNPVLATIPS TAVYQNQNST PLFVPNSPSL SMLFSDVMRQ
AGVAPRDISL VEAHGTGTPV GDPAEYESIR TALGGPRVGR TKPLPIGSVK GHIGHTEGAS
GAIALIKVIM MMRGGFIPPQ ASFTKMSHNI AVRPDDMMEV VTQLRPWADP HKIALLNNYG
ACGSNASLIV AQPPPALRAP TRGAHQHPEG RRYPFWIAGL DARAISAYAA KLIRYLPSSP
QDIPTLADIS FSMNRQSNRG LAQGFVFSSR SVAELQEKLA QAAGAAGKEA AALVGIEPVR
AERPVVLCFG GQVSLFVGLD RALFDSAAVL RRHLDECDAA VTALGLDSIY PGIFEREPVQ
DTVKLQTMLF AMQYASAKSW MDCGLQGKVA AVVGHSFGEI TALCVAGVLS LEDTIKLVAA
RARLVRDSWG PDPGAMMAVE ADEGLVRELL QEANRSSDGS AGIACYNGPR SFTLAGSTSA
VDAVQATMSA DAKFKAIRSK RLNVTNAFHS ALVEKLVDSL GQVGKELTFH PPTIPVERAT
ETPFDAASMD WTFVPRHMRE PVFFNHAVQR LAKQHPQAIF LEAGSNSTIT IMASRALAQS
QTSPPDAHHF QAVSITTATG FDGLTDATVA LWKQGLRVAF WAHHALQTLE YAQLLLPPYQ
FDTSPSSRHW LEMKSPQKVI DKAVKALVAA GTPHQLPQNQ TIDPKTLPLW TFVGYQDAPT
NKTARFRINT ESAQYNTYVL SHVIAQTAPI CPGTLECDMM IEALFSLHAD AQENGLQPEI
RDLVNHTPIC VDPSRTVYLE LTALYKKRTQ WSAHFLSVAN GGGDAHNPQT HAEARLRLRA
AGDADYLREF AQFERLVSHG RCRELLGLGL DVEGVEVLQG RGVYRAFDPV VEYGEVYRGV
RYLVGRGNEC AGHVQLPARH RGDTWLDVAL SDSFSQVGGL WVNLMTDVPP GDMYIATGCE
VTMRAPRATA RGEGDVWHVY GRHARQSDKA YTTDLFVFDA ATGSLVEVML GLQYGRVAKA
SMSRMLARMT TDETVVRTKA SLPQLPATNS SPPATAPAPA MAVVEASRNS KKRSKKTEKK
EAKPKKTQKD SGWRDITEEV RNLVAHVSGI EASEIGLDSE MADFGIDSLM GMELGREVEL
TFKCKLDQAE QMEATSLRKF VAVVAKALFG TDQPAEVEDE ASEAEDEDDD DSSSTGEGGT
WSEPSQEDGS KESSGLQTPD SSSYTPPPEK AQKAGPVPGN LKPLNAPTAP PAVSNLVLSP
ADVLAAFGEV KMATDSLMRE YEIDKTERTL LAGSNRLCAA LVVEALDELG CPIGTAAAGQ
PLERVPFLPQ HGRLMQCVYE FLERDARLID IDVASGQLTR THVAAPRKTS QAILEDLLTS
QPEFAVANRL AYHAGKQLAG VLSGKTDGIR VLFGSPEGRE VTAAMYCEHP FNRMSYRQMS
DVVEGLAERI QSRGGTGETF KVLEMGAGTG GTTLVMAPLL ASLEARGIMR VEYTFTDLSP
SLVANARRRF GKMYPFMRFA VHDIEKSPAE ELRGQHLVLA SNAIHATHNL VVSASNVRQA
LRPDGFVMIL EMTEVVPFID LVFGLLEGWW LFDDGRNHAV VPAEHWEREL HTAGFGHVDW
TDGNLPENAV QKVIFAMASE PQGPRLPKAA PEQTMELDRG DVAARTAEAE RLVTKYSNAW
ATPRLQALAA RRETNQGQPK RNKANLGAVV LVTGATGSLG SHLVQKLAEN PEVAQVVCLN
RRSSSGLSAV KKQQEAFASR GITLSPGARA KLRVLDADTS QAQLALPPHE YTWLLQHGTH
IVHNAWPMSG TRPISAFEPQ LQGMRNLLDL AREMATRDAV HPFRVGFQFV SSIGVVGYAG
EPRILEDRVP LSAVLPSGYG EGKWVCERLL DDTLHKYPSL FRPMVVRPGQ ISGSSNSGFW
NPVEHFAFLV KSAQTLRAWP DFDGVLQWIP VDHCASVMAD LLKMGVADAP DAYPVYHIDN
PVGQQWKAMS PVLAAALDIP PHAIIPFSSW IKRVRRSPLL AETENPAARL VDFLDSHFER
MSCGGLILDT TKAKEHSQTM AKEGPVDPDL ARLYVAAWKK MEFLRS
