ID ANDM_EMEVA Reviewed; 2430 AA.
AC A0A097ZPE0;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 07-JAN-2015, sequence version 1.
DT 27-NOV-2024, entry version 39.
DE RecName: Full=Non-reducing polyketide synthase andM {ECO:0000303|PubMed:25216349};
DE EC=2.3.1.- {ECO:0000269|PubMed:25216349};
DE AltName: Full=Anditomin synthesis protein M {ECO:0000303|PubMed:25216349};
GN Name=andM {ECO:0000303|PubMed:25216349};
OS Emericella variicolor (Aspergillus stellatus).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Nidulantes.
OX NCBI_TaxID=1549217;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND CATALYTIC ACTIVITY.
RC STRAIN=ATCC 12069 / CBS 136.55 / IMI 60316 / NBRC 32302;
RX PubMed=25216349; DOI=10.1021/ja508127q;
RA Matsuda Y., Wakimoto T., Mori T., Awakawa T., Abe I.;
RT "Complete biosynthetic pathway of anditomin: nature's sophisticated
RT synthetic route to a complex fungal meroterpenoid.";
RL J. Am. Chem. Soc. 136:15326-15336(2014).
CC -!- FUNCTION: Non-reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of anditomin, a fungal meroterpenoid
CC (PubMed:25216349). The first step of the pathway is the synthesis of
CC 3,5-dimethylorsellinic acid (DMOA) by the polyketide synthase andM
CC (PubMed:25216349). DMOA is then converted to the phthalide compound
CC 5,7-dihydroxy-4,6-dimethylphthalide (DHDMP) by the cytochrome P450
CC monooxygenase andK, which is further prenylated by the
CC prenyltransferase andD to yield farnesyl-DHDMP (PubMed:25216349).
CC Further epoxidation by the FAD-dependent monooxygenase andE leads to
CC epoxyfarnesyl-DHDMP (PubMed:25216349). The next step involves the
CC terpene cyclase andB that converts epoxyfarnesyl-DHDMP into preandiloid
CC A through opening of the epoxide ring followed by the cyclization of
CC the farnesyl moiety (PubMed:25216349). Preandiloid A is in turn
CC oxidized at the C-3 hydroxyl group to yield preandiloid B by the
CC dehydrogenase andC (PubMed:25216349). The dioxygenase andA is solely
CC responsible for the dehydrogenation of preandiloid B leading to the
CC enone preandiloid C, as well as for the intriguing structural
CC rearrangement to generate the bicyclo[2.2.2]octane core, transforming
CC preandiloid C into andiconin (PubMed:25216349). FAD-binding
CC monooxygenase andJ then produces andilesin D which is reduced by
CC dehydrogenase andI to yield andilesin A (PubMed:25216349). Action of
CC acetyltransferase andG followed by a spontaneous acetate elimination
CC leads then to andilesin B, which is in turn substrate of the short
CC chain dehydrogenase andH to yield andilesin C (PubMed:25216349).
CC Finally, the dioxygenase andF catalyzes the transformation of andilesin
CC C to anditomin (PubMed:25216349). {ECO:0000269|PubMed:25216349}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=3 malonyl-CoA + acetyl-CoA + 2 S-adenosyl-L-methionine = 3,5-
CC dimethylorsellinate + 2 S-adenosyl-L-homocysteine + 3 CO2 + 4 CoA;
CC Xref=Rhea:RHEA:49628, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57288, ChEBI:CHEBI:57384, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:131856;
CC Evidence={ECO:0000269|PubMed:25216349};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:49629;
CC Evidence={ECO:0000269|PubMed:25216349};
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:25216349}.
CC -!- DOMAIN: Multidomain protein; including a starter unit:ACP transacylase
CC (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes
CC repeated decarboxylative condensation to elongate the polyketide
CC backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and
CC transfers the extender unit malonyl-CoA; a product template (PT) domain
CC that controls the immediate cyclization regioselectivity of the
CC reactive polyketide backbone; and an acyl-carrier protein (ACP) that
CC serves as the tether of the growing and completed polyketide via its
CC phosphopantetheinyl arm (PubMed:25216349).
CC {ECO:0000250|UniProtKB:Q5B0D0, ECO:0000305|PubMed:25216349}.
CC -!- DOMAIN: The release of the polyketide chain from the non-reducing
CC polyketide synthase is mediated by the thioesterase (TE) domain
CC localized at the C-ter of the protein (By similarity).
CC {ECO:0000250|UniProtKB:Q5ATJ7}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AB981314; BAP81867.1; -; Genomic_DNA.
DR AlphaFoldDB; A0A097ZPE0; -.
DR SMR; A0A097ZPE0; -.
DR ESTHER; emeva-andm; Hormone-sensitive_lipase_like.
DR BioCyc; MetaCyc:MONOMER-19041; -.
DR UniPathway; UPA00213; -.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0004312; F:fatty acid synthase activity; IEA:TreeGrafter.
DR GO; GO:0008168; F:methyltransferase activity; IEA:UniProtKB-KW.
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 GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR CDD; cd02440; AdoMet_MTases; 1.
DR CDD; cd00833; PKS; 1.
DR Gene3D; 3.30.70.3290; -; 1.
DR Gene3D; 3.40.47.10; -; 1.
DR Gene3D; 1.10.1200.10; ACP-like; 1.
DR Gene3D; 3.40.50.1820; alpha/beta hydrolase; 1.
DR Gene3D; 3.40.366.10; Malonyl-Coenzyme A Acyl Carrier Protein, domain 2; 2.
DR Gene3D; 3.10.129.110; Polyketide synthase dehydratase; 1.
DR Gene3D; 3.40.50.150; Vaccinia Virus protein VP39; 1.
DR InterPro; IPR029058; AB_hydrolase_fold.
DR InterPro; IPR001227; Ac_transferase_dom_sf.
DR InterPro; IPR036736; ACP-like_sf.
DR InterPro; IPR014043; Acyl_transferase_dom.
DR InterPro; IPR016035; Acyl_Trfase/lysoPLipase.
DR InterPro; IPR049492; BD-FAE-like_dom.
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; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR049552; PKS_DH_N.
DR InterPro; IPR049900; PKS_mFAS_DH.
DR InterPro; IPR050091; PKS_NRPS_Biosynth_Enz.
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 PANTHER; PTHR43775; FATTY ACID SYNTHASE; 1.
DR PANTHER; PTHR43775:SF21; NON-REDUCING POLYKETIDE SYNTHASE AUSA-RELATED; 1.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF20434; BD-FAE; 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; PF21089; PKS_DH_N; 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 SUPFAM; SSF47336; ACP-like; 1.
DR SUPFAM; SSF53474; alpha/beta-Hydrolases; 1.
DR SUPFAM; SSF52151; FabD/lysophospholipase-like; 1.
DR SUPFAM; SSF55048; Probable ACP-binding domain of malonyl-CoA ACP transacylase; 1.
DR SUPFAM; SSF53335; S-adenosyl-L-methionine-dependent methyltransferases; 1.
DR SUPFAM; SSF53901; Thiolase-like; 1.
DR PROSITE; PS50075; CARRIER; 1.
DR PROSITE; PS00606; KS3_1; 1.
DR PROSITE; PS52004; KS3_2; 1.
DR PROSITE; PS00012; PHOSPHOPANTETHEINE; 1.
DR PROSITE; PS52019; PKS_MFAS_DH; 1.
PE 1: Evidence at protein level;
KW Methyltransferase; Multifunctional enzyme; Phosphopantetheine;
KW Phosphoprotein; Transferase.
FT CHAIN 1..2430
FT /note="Non-reducing polyketide synthase andM"
FT /id="PRO_0000436589"
FT DOMAIN 377..793
FT /note="Ketosynthase family 3 (KS3)"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT DOMAIN 1260..1568
FT /note="PKS/mFAS DH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT DOMAIN 1614..1688
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 9..247
FT /note="N-terminal acylcarrier protein transacylase domain
FT (SAT)"
FT /evidence="ECO:0000255"
FT REGION 346..371
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 897..1194
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 1260..1389
FT /note="N-terminal hotdog fold"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT REGION 1265..1567
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255"
FT REGION 1417..1568
FT /note="C-terminal hotdog fold"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT REGION 1840..2072
FT /note="Methyltransferase (CMeT) domain"
FT /evidence="ECO:0000255"
FT REGION 2093..2430
FT /note="Thioesterase (TE) domain"
FT /evidence="ECO:0000250|UniProtKB:Q5ATJ7"
FT ACT_SITE 542
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 677
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 716
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01348"
FT ACT_SITE 984
FT /note="For acyl/malonyl transferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 1295
FT /note="Proton acceptor; for dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT ACT_SITE 1475
FT /note="Proton donor; for dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01363"
FT ACT_SITE 2216
FT /note="For thioesterase activity"
FT /evidence="ECO:0000250|UniProtKB:Q5ATJ7"
FT ACT_SITE 2367
FT /note="For thioesterase activity"
FT /evidence="ECO:0000250|UniProtKB:Q5ATJ7"
FT ACT_SITE 2399
FT /note="For thioesterase activity"
FT /evidence="ECO:0000250|UniProtKB:Q5ATJ7"
FT MOD_RES 1648
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2430 AA; 265244 MW; 5A07340105952070 CRC64;
MEASQGIAVL FGPQSADIEE AVSCIQAFVR ENPSATYLID IIQSLPSIWP AIQDSWVPLA
QIDGKRQLET LGSLFGGGAA TVPPKSSNIL ITPLTVLQHI VELCRLRKRG SSLQIKDVQG
FCVGFLAATA VASAHDETQF RSIVAKVIRL AVCVGALVDL NELERGRAAS LAVRWSGEEG
YSCMEKVLAA HPEAYISCLT DTNRATITVP QELQRDIIRE MANQGLSVRS IPLCGRFHHP
DHAPAVRQLM QLCRSDDRFQ LPDSKTLQFP LRSNIDAELV PEGPLHDIAL QSILCLQSKW
HATVSAALES LTERNGNVPI AAIGPEQCLP RTARSRLRQT WGSTLVPMGT GHTVNGNLTP
SRATSPADSS SELIPTVQPI AITGMSCRYP QADSVEALWE LLELGKCAVG PLPNKRFRMD
ELLREPNGPF WGNYLEEPDV FDHRFFGISA REAATMDPQQ RLLLQVAYEA MESAGYCGIR
SSQVPEDVGC YIGVGSDDYT DNVGSTHANA YSAPGTLQAF NTGRISHHFG WSGPSVVVDT
ACSSAAVAIH MACQGLYTGD CSIAVAGGVN VMTSPKVTQN LAAASFLSPT GASKAFDASA
DGYCRGEGAG LVVLRPLDQA LQNGDPVLGI ITGTAVNQGS NCSPITVPVS RSQMSLYRKA
LSASGVSPDD VTYVEAHGTG TQVGDPIEMD SIRNTFGGTH RTEQLYVGSI KDNVGHTETS
SGVAGLIKTI LMLQKQTIPK QANFSRLNPK IPALDMDNVV IPTRSTDWKV STRVAMVTNY
GAAGSNASII VRQPFTYPGG TRTTLSHAPI FIAAKTAESL RTYCDNLLAS LRQIPVLPDH
LVSDYAYNLA TKQNRTMDCY IGFATDSPAS LTNQLAAVAS GAREVYSRSG KALPVVLCFG
GQNGNIVHIS QDLYTNTHLL QFHLADCEKA CQSLGLPSLF PTIFRADPIE DLVSLHSALF
ATQYATAKCW IDSGLEVDRM IGHSFGQLTA LCVAGGLSLV DALRFISERA RLLEKHCSGK
RGLMLSVEAS EEDVRGLVNG AGQAVDVTCY NGPRSFVIGG EKVAIEAFEK VATGFKTQRL
ANTHAFHSHL MDPILPALRE VAQSMTFQPT TIPVEACSQD MEWTFVHAAQ LVTHTRQPVY
FESAVRRIAN KYPTGAVWLE AGSASPVIPM IRRVVESSPN NHVYQPIDIR PPQAIANLSK
ATSGLWSNGT HVQFWPFHKS QSNCYNSINL PPYQFTKTRH WIDYDPLAFM PSSAPKDAGP
EEAKKLVQLL KQQSGECLFT INTKDLLYQT CTKGHAVVNQ NLCPASLYLE MVISAASHVC
PVELSSTMPH VQNLCILAPL VLNPQGELQL RLSQQNGERD QWTFSLFTQQ GQTSTVHATG
TIWLHAITNS SAIVSRFRSL NRLMIPSRPD SIENSPRSSG LKGAAIYQSF RRVVNYAEYY
RGVENVFALT NEATGQVKID TALVKDSCCD PILIDNFIQV AGIHVNCLSE MSEDEVYVCS
AVGEIFIGEA FMQRDCGASL SWRVYSNYDR LSRNQVACDV FVMNQESGQL AIAIMGATFT
GVSIRALTRT LARLNNQQSS APEVHDAPIP QDTVRADAMP AATPAPLPST LQEVDNLPAV
QGMLGDLLGV GLEELAPSCS LLEIGVDSLM STEVLTEIKK RFNVNITSAA LSEIPDIGGL
VQVIFPGTSV SQTTVSQTAP NDSNAVVVES TPVGELSMLV QEAYDAFDAI RSMTDYSRET
KWTGFYDIVF PKQMALVTAY VVEAFQALGH PLQSISAGGE VPLIPVLPQH EKVRNQFYAV
LEFSRLVSRT TDGRIVRTKE QIPTEAASNL HDEIIRQFPH HASEHMLLRT TGSQLAECLS
GDANPLALLF QDAEARRLMG DVYTNAPMFK SATMHLAGYL QGVLERVGSG RTVKILEIGA
GTGGTTRYLV SQLAARGLRF EYTFTDISSS LVMLAKKGFK EYDFMRYMTL NIEQDPPQEL
LGQYDIIIST NCIHATRNIA YSCSNIRRML RPDGILCLIE LTRNLFWFDL VFGLLEGWWL
FDDGRKHALA SEHLWNETLD KAGYSWIDWS RNDLKESEFL RLIVASPSKP EMPLVTQETV
KFDEKDGVSL LADIYYPSVA DDANQRRPIA LLLHGGGHIM LSRKDIRADQ TMLLLDAGFL
PVSIDYRLCP ETSLIEGPMR DARDALRWAR QTLPTLQLQR EDIHPNGDQV VAIGWSTGGH
LAMSLAWTAA ELAVAAPEAV LSFYCPTDYI DPFWSQPNFP FGKQIAPPGE IDIRAGMSPN
PITAYNPPRS KRALGGWMST TDPRSRIALH MNWKGQTLPV LLNAAKTAPG EMLLDPTKED
IVRVCPTSQA SAGNYRSPTF IIHGSLDDLI PMSQVRHTAK VMKANGVDVH LRELEGSIHL
FDIASTYGDK PDEVQAVADG IQFLKDRVQC
//
