ATNH_ARTSZ
ID ATNH_ARTSZ Reviewed; 2466 AA.
AC A0A455LLX1;
DT 02-JUN-2021, integrated into UniProtKB/Swiss-Prot.
DT 05-JUN-2019, sequence version 1.
DT 03-AUG-2022, entry version 17.
DE RecName: Full=Highly reducing polyketide synthase atnH {ECO:0000303|PubMed:29797385};
DE Short=HR-PKS atnH {ECO:0000303|PubMed:29797385};
DE EC=2.3.1.- {ECO:0000269|PubMed:29797385};
DE AltName: Full=Arthripenoid biosynthesis cluster protein H {ECO:0000303|PubMed:29797385};
GN Name=atnH {ECO:0000303|PubMed:29797385};
OS Arthrinium sp.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Xylariomycetidae; Xylariales; Apiosporaceae; Arthrinium;
OC unclassified Arthrinium.
OX NCBI_TaxID=1756131;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], DOMAIN, FUNCTION, CATALYTIC ACTIVITY, AND
RP PATHWAY.
RC STRAIN=NF2194;
RX PubMed=29797385; DOI=10.1002/anie.201804317;
RA Zhang X., Wang T.T., Xu Q.L., Xiong Y., Zhang L., Han H., Xu K., Guo W.J.,
RA Xu Q., Tan R.X., Ge H.M.;
RT "Genome mining and comparative biosynthesis of meroterpenoids from two
RT phylogenetically distinct fungi.";
RL Angew. Chem. Int. Ed. 57:8184-8188(2018).
CC -!- FUNCTION: Highly reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of the meroterpenoids arthripenoids
CC (PubMed:29797385). The pathway begins with the HR-PKS atnH that
CC catalyzes two chain-extension steps to form a reduced triketide, which
CC then primes the SAT domain in the NR-PKS atnG to initiate three more
CC cycles of extension to give a linear hexaketide corresponding to the
CC polyketide part of arthripenoids (PubMed:29797385). The FAD-dependent
CC monooxygenase atnJ then performs an oxidative decarboxylation at C11 of
CC the atnH/atnG product, via an electrophilic aromatic hydroxylation with
CC concomitant ipso-decarboxylation (PubMed:29797385). The membrane-bound
CC polyprenyl transferase atnF then introduces a farnesyl group before the
CC FAD-dependent monooxygenase atnK functions as the first epoxidase on
CC terminal C12'-C13' olefin, followed by a second epoxidation on C7'-C8'
CC catalyzed by atnA (PubMed:29797385). The terpene cyclase/mutase atnI
CC then initiates the sequential tricyclic ring formation through
CC protonation of the terminal epoxide and catalyzes the regioselective
CC and stereoselective 6/6/6-tricyclic ring formation (PubMed:29797385).
CC The cytochrome P450 monooxygenase atnM is responsible for hydroxylating
CC both C1' and C10' (Probable). The next steps may involve ketoreduction
CC and acetyl transfer by the ketoreductase atnB and the acetyltransferase
CC atnC, and lead to the production of arthripenoid B, the final
CC biosynthetic product of the atn cluster (PubMed:29797385). The
CC hydroquinone moiety in arthripenoid B is prone to undergo spontaneous
CC oxidation to afford a benzoquinone compound, a key intermediate for
CC generating structure diversity (Probable). For instance, addition of a
CC cysteine followed by ring contraction gives arthripenoid A,
CC tautomerization gives the main product arthripenoid C, addition of a
CC molecular of water or amine affords arthripenoid D or E, respectively,
CC and loss of one water forms arthripenoid F (Probable).
CC {ECO:0000269|PubMed:29797385, ECO:0000305|PubMed:29797385}.
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:29797385}.
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:29797385}.
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DR EMBL; MH183014; AYO60881.1; -; mRNA.
DR AlphaFoldDB; A0A455LLX1; -.
DR SMR; A0A455LLX1; -.
DR UniPathway; UPA00213; -.
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 GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
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; 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; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 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; 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.
PE 1: Evidence at protein level;
KW Acyltransferase; Methyltransferase; Multifunctional enzyme; NADP;
KW Oxidoreductase; Phosphopantetheine; Phosphoprotein; Transferase.
FT CHAIN 1..2466
FT /note="Highly reducing polyketide synthase atnH"
FT /id="PRO_0000452560"
FT DOMAIN 2370..2452
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 13..431
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 525..829
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 891..1175
FT /note="Dehydrogenase (DH) domain"
FT /evidence="ECO:0000255"
FT REGION 1343..1522
FT /note="Methyltransferase (CMet) domain"
FT /evidence="ECO:0000255"
FT REGION 1735..2052
FT /note="Enoyl reductase (ER) (ER) domain"
FT /evidence="ECO:0000255"
FT REGION 2077..2251
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255"
FT REGION 2323..2351
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 2324..2339
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 180
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2412
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2466 AA; 267554 MW; 0137C9010B0EA1BF CRC64;
MTITKVGSAP SPIAIVGIGL RLPGGCHDAK SYWDLLVNQK DARRSIPPER FNIDGFHGKA
PGAGNLSMKH GYFLDEPVDR FDAAFFSMSQ AEVARVDPQQ RLLLEVMHEA LENAGEVNFR
GSDIAVYAGS FGQDWLQMQA RDMQEGNVYD MTGMDDFVFA NRVSYELDLH GPSMTVKAGC
SSSLIALHLA CEALKRGDCS GALVGASNLL LSPEYFLALD GLGALSPDGS SRAFDAFANG
YARADAVNAV YVKTLDDALR DGNPIRAIIR STAVNADGKT VGLTNPSTDA QASLIRRAYQ
KAGIYNPEET PMVECHGTGT ATGDPQEVAA VVQIFGDQQT YIGSVKPNIG HGEGAAGLSS
LIKSVLSLER QTIPPNIKFQ TPNPKIPFAE ANLVVPTVAV PWPEGRDRRI SVDSFGLGGA
NAHVIIEADP STRGRKGVPH MNGNCKHVYS QRLLPFSAHT ETSLKAMLDK YESFMESETF
KVTDLAYTLG ARRHHHKFRS FCVTDGLSFQ PAATVRKPEK GGLLYIFTGQ GAQWSGMGRE
LIRDFPSFRG DIQQMDKYLS VCLFPPAWRM EDVLSNAEII NAAEYAQPLC TAIQIALINL
LRSWNIHPDG VVGHSSGEIA AAYAAGALTM EDAILVAFYR GAASSQQTRP GAMAAVGLGR
DEVSGLLSSG ATIACENSRS SVTISGDLSA VEDTLDRVRQ YRAEALARKL KVDRAYHSDH
MISVGRIYRE LISTVTTSHG SLPIPFFSSV TGDETRDASL LGPNYWKSNM ENPVLFLSAV
ESALESTHDF GMALELGPHS ALSGPFRQIC KDRSKTITYD SCLTRASDCT KSLLTAAGGL
FCQGVMVDFA AMNPGGTTMS SLPPYPWTHD TSYWHESRIS REFRTRAHPE HELLGARVIG
GNDLEPSWRK MLSLKEVPWL SDHIVADDVV FPAAGYITMA TEAIRQISSH PSSFTIRALS
IGSAMPLHNG KTTEIMTRLQ PHRLTDNHDS AWFDFSVMSY DGHRWTRHCS GEIRTADASA
LSATGSKSSA TEGQREVATA KWYQAAKSVG LEYGPAFQGL QDVSYDVSRG CTSAKLRSME
QYYGLLHPST IDQLLQCCIL GSVKGHERLM NRTALPVYIE EMSIGTGDNL EDLQCDAYTV
LSGQDSFSAH GHIETRGGTR ALQAKGVQFR QLGIHTSTDK DPLKELHLLE WRPDIDFTPL
DQMVHQTEDL SSCLELVERL NILCMLETTR LLKPLDSSQH HFQRFKESTE EFVDNLRRNG
NRMVKDLDQI LDIAPEKRAS AIKALTEEAL ATPARDIALA VVRIFNDVEN IFTGSVEPLT
VLLKDNLLME FYNFFNMLNH RDFFQLLGHK HRGTLRVVEI GAGTGGFTST ILPALTDAAG
GSLFSTYTYT DISSGFFKAA KERFGEYSGI EYAVLDISKD PASQGLELGS YDLVVAANVL
HATPYLVETM TNCRSLLRPG GRVFMLELST EAKWVNYVMG TLPGWWLGEP DGRPNEPYIK
SEQWDVVLQK SGFRNVTAVA DQKPPYQLDD IIVAIADDDV ATPSKALSLL VRDPSQPTAV
SNAILSEFSQ AGYDVSLCSL REPPTSPVDT VSLLDIDGPR SFFEDLDEKG LRGLIRFITQ
SRGQKMLWLT GPAQVGAENP HHAMVLGLAR TLRLELGSYF ATMELDISAD PSAFGLVVKV
FDQIQRQSKR DVVDYEYALV NGTVQVPRYV TCTAGQVVTT PDAQVHRKLH VGKPGILASL
QWQEGMGDFP LKEGEVEINV RSSAVTHQDV LLASGAVHDK EGLGFECAGI VSRINAGTST
SGTDLQVGDR VLCWSSGSLA THARVDSRCC IKLPDGLSFN DAVTMPTAYA TMIRGLLDNS
SLATGDTVLI HSGCSPMGLA AIQIARMQGA EIFVTARTEA EKEFLVTEQG VPTSHVFSSL
DTSFVAGIMQ ATNARGVDVV VNLLSGDLMH ESWKCVAAGG NMIDLSSKDI TGHGRLDMTM
FGGNRGFHGI DIPNLITQKP SLAPRLLKTT MDLYTAGTIK PIGPISLYTP RNIKQAFHHL
HGEDVPIGSV VVEFSDDAQS LPAESYSDEI EFRKDRSYVL IGGLGGLGRS AAVWLAERGA
GCIIFLSRSA SAGAENQSLV SELKALGCET QIATGSVTDA VAVDKLVANA AKPIGGVLHL
ALVLKDEALL DMTFDSWQGA TEAKVQGTWN LHRALEGQPL DFFVLASSIY GVQGNPKQAN
YAAASTFLDA FVQFRQKLGL PASVIDLGVM EDVGYVSQHP AILENLRRAG AQLLCENDFL
RSLQLGIRTS SVPAPLIPTD LTSGYVNRAQ FVVGLGQHPP DARGLGLKRA KDSHHQGAGK
SATEQDSTGE DGDALRRFLE NAKRDPSSLD DEAGVTQFLA AQVAECLEGL LIFGDSSGLD
LGLGLEDLGV DSLVAIELQS WWIESFATHI TILELTKSAS ITELGKLARG RMLETFHGQN
GEPVMA
