NTNH_NECSZ
ID NTNH_NECSZ Reviewed; 2371 AA.
AC A0A455M2Y3;
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 ntnH {ECO:0000303|PubMed:29797385};
DE Short=HR-PKS ntnH {ECO:0000303|PubMed:29797385};
DE EC=2.3.1.- {ECO:0000305|PubMed:29797385};
DE AltName: Full=Nectripenoid biosynthesis cluster protein H {ECO:0000303|PubMed:29797385};
GN Name=ntnH {ECO:0000303|PubMed:29797385};
OS Nectria sp.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Sordariomycetes;
OC Hypocreomycetidae; Hypocreales; Nectriaceae; Nectria.
OX NCBI_TaxID=1755444;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], DOMAIN, FUNCTION, AND PATHWAY.
RC STRAIN=Z14-w;
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 nectripenoids A
CC and B, as well as cochliquninone D and isocochliquninone E
CC (PubMed:29797385). The pathway probably begins with the HR-PKS ntnH
CC that catalyzes two chain-extension steps to form a reduced triketide,
CC which then primes the SAT domain in the NR-PKS ntnG to initiate three
CC more cycles of extension to give a linear hexaketide corresponding to
CC the polyketide part of nectripenoids (Probable). The FAD-dependent
CC monooxygenase ntnJ then performs an oxidative decarboxylation at C11 of
CC the ntnH/ntnG product, via an electrophilic aromatic hydroxylation with
CC concomitant ipso-decarboxylation (Probable). The membrane-bound
CC polyprenyl transferase ntnF then introduces a farnesyl group before the
CC FAD-dependent monooxygenase ntnK functions as the first epoxidase on
CC terminal C12'-C13' olefin, followed by a second epoxidation on C7'-C8'
CC catalyzed by ntnA (Probable). The terpene cyclase/mutase ntnI then
CC initiates the sequential tricyclic ring formation through protonation
CC of the terminal epoxide and catalyzes the regioselective and
CC stereoselective 6/6/6-tricyclic ring formation (Probable). The
CC cytochrome P450 monooxygenase ntnM may then hydroxylate C1' (Probable).
CC {ECO:0000269|PubMed:29797385, ECO:0000305|PubMed:29797385}.
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000305|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}.
CC -!- DOMAIN: The lack of conserved catalytic residues in the ER domain
CC supports the fact that nectripenoids retain an alkene at C2-C3.
CC {ECO:0000305|PubMed:29797385}.
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DR EMBL; MH183001; AYO60868.1; -; mRNA.
DR AlphaFoldDB; A0A455M2Y3; -.
DR SMR; A0A455M2Y3; -.
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; 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 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 2: Evidence at transcript level;
KW Acyltransferase; Methyltransferase; Multifunctional enzyme; NADP;
KW Oxidoreductase; Phosphopantetheine; Phosphoprotein; Transferase.
FT CHAIN 1..2371
FT /note="Highly reducing polyketide synthase ntnH"
FT /id="PRO_0000452558"
FT DOMAIN 2280..2362
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258,
FT ECO:0000305|PubMed:29797385"
FT REGION 13..432
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29797385"
FT REGION 528..796
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29797385"
FT REGION 858..1142
FT /note="Dehydrogenase (DH) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29797385"
FT REGION 1309..1456
FT /note="Methyltransferase (CMet) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29797385"
FT REGION 1669..1968
FT /note="Enoyl reductase (ER) (ER) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29797385"
FT REGION 1993..2167
FT /note="Ketoreductase (KR) domain"
FT /evidence="ECO:0000255, ECO:0000305|PubMed:29797385"
FT ACT_SITE 180
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 2322
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 2371 AA; 258694 MW; 0462AACDE93264BA CRC64;
MIVPETRPGP SPIAIVGIGL RLPGGCHDAQ SYWDLLVHQK DARKPIPPER FNIDGFHKES
DGVGSLSMRH GYFLDEPADR FDAGFFSMSQ TEVARVDPQQ RLLLEVMHEA LENAGEVGWR
GSNIAVYAGS FGQDWLQMQA RDPQDGNVYG ITGMDDFVLA NRVSYEFDLH GPSMTVKAGC
SSSLIALDLA CEALQRGDCS GALVGASNLL LSPEYFLALD NLGALSSAGS SNTFDTNASG
YARADAVNAV YVKRLDDALR DGNPIRAIVR STAVNSDGKT VGLTNPSTDA QARLIRRAYE
KAGIINPGET PVVECHGTGT ATGDPQEVAA VVQVFSVMKL TQIPQVKPNI GHGEGAAGLS
SLIKAVLSLE RNTIPPNIKF TTPNPKIPFT EARLVVPTKA TPWPKGRSRR ISVDSFGLGG
ANAHVILEGY STTPSPHRNG IPKVNGHTKT STLQRLLVFS AHNETSIAKM TSNYQAFTES
ESYRVKDLAY TLGARRSHHK WRSFCITDGK SLQPTPAVRS SDPKGLLFIF TGQGAQWSDV
LLNSQEISSA EYAQPLCTAI QIGLTNLLRE WKITPDGVVG HSSGEIAAAY AVGALEMRDA
IHVAFYRGVA SSQQKRPGAM AAVGLGRHEV SNLLSAGTTI ACENSRSSVT ISGDYDAVED
TLDRVRQYWP DALARKLKID RAYHSDHMRS VGILYEELIS EIKTSTKSLT IPFFSSVTGQ
ATYDASLLGP TYWRANMERP VLFLSAVENA LDSMQEFGLA LELGPHSALS GPFRQICKEL
DKRIIYNSCL SRGADATTTI LTAIGQLYCQ GLAPDFSALN PGGVTMSNLP PYPWTHDASY
WNESRISREF RTRPHPEHEL LGARVIGGND MEPSWRKLLN LKEVAWLSDH VVAEDVVFPA
AGYVAMAGEA IKQITGTAGF TIRSLSIGSA MPLNNARATE IITRLQPHRL TDDQDSTWFD
FSVMSYDGNT WTRHCNGKVH PGNASTLSME EKKSSPAEDG VRGVISAKWY QAAKAAGLEY
GPTFQGLQDA SYNVTRDCIS STLQTPLQTS SVLHPTTMDQ LLQCCILGSV KGHLRLMSKL
VLPVHIDEMY IADSHSFEGL YCETHSDFTG ADMMEARGHI RVGNGSLALQ AKGIRFRILE
NNRSKENALQ ELRLLEWRPS IDLVDLRQLV QQTTDLSGCL ELVERLNILC VLGTTRILKS
MENTQHHFKR FKEWNEEYVN NIRLNGSNVV QDTDHIFEMT SAECEFAIKE LTAEALETPA
RDIALAITRI FYDVENIFTG AAEPLAVLLR DDLLMKIYNF FNMLDHRHFF QLLGHNKKTL
RIIEIGAGTG GFTSTIVPAL TDSAGGCLFS TYTYTDISSG FFKAAKERFS EYPGIEYTVL
DISEDPASQG LELNSYDLVV AANAKAKWVN YIMGTLSGWW LGEPDGRINE PYIQAQQWDD
ILQKAGFENV TAIMDQSPPF QLDNIVIANA VDDALAPPKA LSLLVPDTTQ VAGPAAELVS
KFQSEGYEVS LCSLWDLPTA PLDIVSLLDI MEPQTFFQGL TDRDLRGLIR FITHTHGQKL
LWLTGPAQIS TKDPHSAMVL GFARTLRLEL GTIFATMELD IAAEPSPWNS VVEVFAKLQS
QGTDDLVDCE YALVDGTVQV PRYITRSSEA VLPVASEQIS RQLHVAKPGL LSSLQWQGSS
REAELKEGEL EIAVRASSVN YQDALLALGH VHSNHGLGLD CAGIVTHINS RAGKDNLQVG
DRVLCWSAGS LSTHVRADSQ RCIKIPDTLN FDVAVTMPTT YGTMIRGLIE IDAMGVAAIQ
IARMQGAEIY ATAATEEEKH FLTTEHDIPM SRIFSSQDNS FVTAIMHDTQ SRGVDIVVNS
LSGELLHESW KCVAEGGNMI DISGKDVSGH GKLDMALFNG NRGFHGLDMA SLVSKKPSLT
RRLLEASIKL YTDGLVKPIR PITRFSTSDV KHAFHQFQGH RPIGAICIEF PDDPLSFPID
SFDDKTRFRE DRSYVLIGGL GGLGRSAAVW LAERGAGSII FMSRSASPSV ESTSLVRELK
ALGCEVQIFT GSVTDASAVE NLVANAAKPI AGMLHLALVL KDEAVLDMTF DSWQGATEAK
VQGTWNLHNA LKDQPLDFFI LLSSIYGVQG NPKQANYAAA STFLDAFVQF RQQLGLPASV
IDLGVMEDIG FVSQHPTILE NLRRAGAQLI RENDFIGALQ LAVRASSQPA PAPPTLASGY
VNRAQFVVGL GQHPPDARGL GLKVDGTIQG QNNTQAVAKE DGDALKQFME NATRDPSSLE
DETAVAEFLA AQVAECLKTL LIFSDSSDLN LKLGLAELGV DSLIAIELQT WWIQNFATNV
TILELTKSAS VMDLGKLARS RILEELHGRD G
