APMLA_ARTPE
ID APMLA_ARTPE Reviewed; 2466 AA.
AC P0CU84;
DT 18-SEP-2019, integrated into UniProtKB/Swiss-Prot.
DT 18-SEP-2019, sequence version 1.
DT 03-AUG-2022, entry version 10.
DE RecName: Full=Highly reducing polyketide synthase apmlA {ECO:0000303|PubMed:31180682};
DE Short=HRPKS apmlA {ECO:0000303|PubMed:31180682};
DE EC=2.3.1.- {ECO:0000269|PubMed:31180682};
DE AltName: Full=Phaeospelide A biosynthesis cluster protein apmlA {ECO:0000303|PubMed:31180682};
GN Name=apmlA {ECO:0000303|PubMed:31180682};
OS Arthrinium phaeospermum (Gymnosporium phaeospermum).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Xylariomycetidae; Xylariales; Apiosporaceae; Arthrinium.
OX NCBI_TaxID=112178;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], DOMAIN, FUNCTION, CATALYTIC ACTIVITY,
RP AND PATHWAY.
RX PubMed=31180682; DOI=10.1021/acs.orglett.9b01674;
RA Morishita Y., Zhang H., Taniguchi T., Mori K., Asai T.;
RT "The discovery of fungal polyene macrolides via a postgenomic approach
RT reveals a polyketide macrocyclization by trans-acting thioesterase in
RT fungi.";
RL Org. Lett. 21:4788-4792(2019).
CC -!- FUNCTION: Highly reducing polyketide synthase (HR-PKS); part of the
CC gene cluster that mediates the biosynthesis of phaeospelide A, a fungal
CC polyene macrolide with a 34-membered macrolactone ring and an all-trans
CC conjugated hexaene structure (PubMed:31180682). The HR-PKS ApmlA uses
CC acetyl-CoA and malonyl-CoA as its starter and extender units,
CC respectively, and provides the large carbon framework in phaeospelide
CC via 16 cycles of polyketide chain elongation, which is the largest
CC number identified in fungal iterative PKSs thus far (PubMed:31180682).
CC During round 1, the KR domain reduces beta-ketone to an L-oriented
CC hydroxy group, while during later rounds, it provides hydroxy groups in
CC the D-configuration (PubMed:31180682). The characteristic conjugated
CC hexaene moiety is built during the later rounds (10-15), when the KR
CC and DH domains are at work but ER is off (PubMed:31180682).
CC Phylogenetic analysis of the DH domain suggests that a polyene
CC formation is programmed in the DH domain (PubMed:31180682). Finally,
CC the mature ACP-tethered carbon chain is transferred to the serine
CC residue of the thiohydrolase apmlB, followed by intramolecular
CC macrolactonization, generating phaeospelide A (PubMed:31180682). When
CC one elongation cycle during rounds 7-9 is skipped, phaeospelide B is
CC biosynthesized instead (PubMed:31180682).
CC {ECO:0000269|PubMed:31180682}.
CC -!- COFACTOR:
CC Name=pantetheine 4'-phosphate; Xref=ChEBI:CHEBI:47942;
CC Evidence={ECO:0000250|UniProtKB:Q9Y8A5};
CC Note=Binds 1 phosphopantetheine covalently.
CC {ECO:0000250|UniProtKB:Q9Y8A5};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:31180682}.
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 group; 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:31180682}.
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DR AlphaFoldDB; P0CU84; -.
DR SMR; P0CU84; -.
DR GO; GO:0016746; F:acyltransferase 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:0009058; P: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 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; IPR013154; ADH_N.
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; 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; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF08240; ADH_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; 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; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 1: Evidence at protein level;
KW Acyltransferase; Multifunctional enzyme; NADP; Oxidoreductase;
KW Phosphopantetheine; Phosphoprotein; Transferase.
FT CHAIN 1..2466
FT /note="Highly reducing polyketide synthase apmlA"
FT /id="PRO_0000447823"
FT DOMAIN 2382..2462
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:31180682"
FT REGION 1..57
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 65..494
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31180682"
FT REGION 608..921
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31180682"
FT REGION 988..1297
FT /note="Dehydrogenase (DH) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31180682"
FT REGION 1737..2061
FT /note="Enoyl reductase (ER) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31180682"
FT REGION 2087..2264
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:31180682"
FT ACT_SITE 235
FT /note="For beta-ketoacyl synthase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 700
FT /note="For malonyltransferase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT ACT_SITE 1020
FT /note="For beta-hydroxyacyl dehydratase activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2422
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2466 AA; 265908 MW; 8F963E348C51EB2E CRC64;
MSDHNHTNGT TNGNGIGSNG VQSHVPNGAH INGTSSGLKP NGISNGTTNG INGHAPSTAA
TQTPVAVVGL ACRLPGKSNS PEALWKFLLD GGVADPTPPD HRYNFSTHYD GSQRPGTMPS
PGGMLLRDVD LTAFDASFFN IGHAEAAVMD PQQRQLLEVT YECLENSGVP LGKLRGTRAG
CVVANNAVEY EGFATHDRED NVSGGSTGFS RSILSNRISH YLDIQGPSIS IDTACSGTLV
GVDLACRYLQ TNQADGMLVG GALLYLDPSA LQDTGPMKGA FSPTGQCHTF DADADGYIRG
EAISCVYLKR LDDAIRDGDP IRAVIRGSAT NSDGNTTSLT QPSSAAQAAA IRMAYSNAGI
SDFNETGYLE CHGTGTPTGD PLEVAGLASV FAPTRPAEKP LIIGSIKSNV GHSESAAGLS
GLIKTVLTVE RGVIPGTPTF IKPTPRIDFD KSRVRPSRRT IRWPQSASGL RRASVNSFGF
GGTNAHVVLE ARDSMIKDPS VRKGFVFSNH GSSLFGLDAD LEAGSERPYI LALSANDKDA
LETNIQTLST HLGDPAVGVK LSDVAYTLSE RRTHHFHRGF VIADSLEISS DSMILGKKKA
QPPRVAFIFT GQGAQWSQMG RDLIESFPLA KATIQKLDAA LQTLPNPPQW SLVDELCEAR
EGAVLRLPEF SQPLVTALQI AQLTVLSHWG ISATRVLGHS SGEIAAAVAA GLVRPEEAIK
IAYLRGLAAK FHQPDQPLGM LAVGVSAEAV APYLETEPTV QIACFNSPTS LTLSGQQPDL
VRVCDRLKAD GHFARMLQVN LAYHSEHIRS IAEEYHSLLK EQVPGAAGSS GNKKVTMFSS
VTGKPISEAY DALGPDYWRQ NMVSPVRFAQ AASNMLSGPE SSEFLIEIGP AGALAGPVAQ
VIKAAPSARN TQYVAAAKRG ADTLLALYET AGKLWANSGV VDLAKVNGYD GQANLVVDLP
NYQWNHSRRY WRESLSASEF LQRPFLSHDL LGSKILSVPW HNPTFYQVIE LSDVPWLRDH
KIGDQVIFPA AGYLSMAVEA IHQTTVMTQW REKGVPKSFA YCLKDVRFLR SLVLEEDVRA
KISLALIPLH ASPRRWYNFR VRSLMEGVWV DHCDGLVRID EEAFDTTAPS RALEPLAHPE
PGAVGYKSAN AGEFSFGPAF QRIEYFDWIW GSPETRAQVT TEYPVSAYSK QSEYPVHPVA
MDCLLQLTGY SIAQMQMNAL DDINCVPVGI EGIVIPSRSN PPAKSCMVRS VAHLLDSSTS
QTYGSRFASA GLYDPEDRSL VMEIKRIRFD PISSRGDQSE HVYMHFGWNA DVSLTDAEGL
NSYLAAAAGS PEEKDLVAVA TPEEQKNDES RSSPFALVQR LLDALAHRRP EMAVLEANLD
SDDSTCLWLD LPSKSNNSGP RSGYSKFHCV SKDPKALSHL QETHNEAPRT TWDLVDMAHP
SGRIDSTDKF DLILVKSSDP ETTFTTPALL SNIVASVSEG GMVILLNTQG KPTVFHDASQ
ALEASGLCRT KDLSASVGGL AIVATARRVG PAATTASGDK VITCFRLTDD DGPSNVLAGL
KDAGWAVNTC SDADALAHRS NILVVDELFT TVASRVTAEQ WKMLQTIIRK ECNVLWVTKG
GQMEVTEPDR AAAPGLLRTI RSEELGIRLI SLDVENPTGP RTLYAIEECL RLLQESHAGI
QKDSEFVERG GVIFTPRLLA DPALNAAKHE PVNGRKPQME SLQDKKTPVC LGVERVGTID
SLHYAERSPT PLPIKDGYIE IEIHAAGVNF KDLALTLGIV NSNDPFTLGG EAAGVVSRIG
KGVPGDRFVA GQRVVAMFPG SFGNRIQVPW QVAHAIPDRL SFEEAATLPV AFLTAMHGLF
DLGNLQAGQR VLIHSATGGT GSAAVQLCQH MGAEIFATAG TEEKRRFLQD IYNIPADHIF
SSRTTDFEHQ IMRLTGGLGV DVILNSLTGD LLEASWNIIA HGGTMVEIGK KDIMEHSRLS
MEPFSRSASF RALDLSLDTA DLYGKGAGLG QTVGRLFERL FSLLERGHVR PITPMQTFAF
GQVTDALALM RSTKHMGKLV LSRGPDSNDQ VAIRPAQRLV RFRPDATYLL VGGLKGICGS
LAVDFAKKGA KHLAALSRSN YDDPQSQIVL RQLKDLDCQI DLLRGDITKV EDVRRVFAET
TVPVAGIIQG AMVLRDRPFA NMTVEEYHAA AACKIQGTWN LHNCAQEAQA PLDFFTILSS
ISSVLGNPAQ GNYASGCSFQ DAFSSYRQEL GLPASTVNLG IIEQIGYMAR NEDLLEKNVS
SEVAKGINER LLCKIIGYSI LQQSGSPVSE DPYSRARMVT GLTMPQPPDS MLRLDARFAA
LFVRDGSSSN TQAGGSGAAS QDVSQEIKEL NLLLRSKSAR AANLPQVVDA TLAVVSGYLV
RAMRLSEAIE PERSLSAYGI DSLAAVEFRN WLRLELGAAM SVIDITTAPS LLFLAEKIIT
KVDGVE
