PYNH_ASPNC
ID PYNH_ASPNC Reviewed; 414 AA.
AC A5ABG6;
DT 17-JUN-2020, integrated into UniProtKB/Swiss-Prot.
DT 12-JUN-2007, sequence version 1.
DT 03-AUG-2022, entry version 71.
DE RecName: Full=Aspartic protease-like protein pynH {ECO:0000303|PubMed:26414728};
DE EC=3.4.23.- {ECO:0000269|PubMed:26414728};
DE AltName: Full=Pyranonigrin biosynthesis cluster protein H {ECO:0000303|PubMed:26414728};
DE Flags: Precursor;
GN Name=pynH {ECO:0000303|PubMed:26414728}; ORFNames=An11g00310;
OS Aspergillus niger (strain CBS 513.88 / FGSC A1513).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus;
OC Aspergillus subgen. Circumdati.
OX NCBI_TaxID=425011;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CBS 513.88 / FGSC A1513 / ATCC MYA-4892;
RX PubMed=17259976; DOI=10.1038/nbt1282;
RA Pel H.J., de Winde J.H., Archer D.B., Dyer P.S., Hofmann G., Schaap P.J.,
RA Turner G., de Vries R.P., Albang R., Albermann K., Andersen M.R.,
RA Bendtsen J.D., Benen J.A.E., van den Berg M., Breestraat S., Caddick M.X.,
RA Contreras R., Cornell M., Coutinho P.M., Danchin E.G.J., Debets A.J.M.,
RA Dekker P., van Dijck P.W.M., van Dijk A., Dijkhuizen L., Driessen A.J.M.,
RA d'Enfert C., Geysens S., Goosen C., Groot G.S.P., de Groot P.W.J.,
RA Guillemette T., Henrissat B., Herweijer M., van den Hombergh J.P.T.W.,
RA van den Hondel C.A.M.J.J., van der Heijden R.T.J.M., van der Kaaij R.M.,
RA Klis F.M., Kools H.J., Kubicek C.P., van Kuyk P.A., Lauber J., Lu X.,
RA van der Maarel M.J.E.C., Meulenberg R., Menke H., Mortimer M.A.,
RA Nielsen J., Oliver S.G., Olsthoorn M., Pal K., van Peij N.N.M.E.,
RA Ram A.F.J., Rinas U., Roubos J.A., Sagt C.M.J., Schmoll M., Sun J.,
RA Ussery D., Varga J., Vervecken W., van de Vondervoort P.J.J., Wedler H.,
RA Woesten H.A.B., Zeng A.-P., van Ooyen A.J.J., Visser J., Stam H.;
RT "Genome sequencing and analysis of the versatile cell factory Aspergillus
RT niger CBS 513.88.";
RL Nat. Biotechnol. 25:221-231(2007).
RN [2]
RP FUNCTION.
RX PubMed=24106156; DOI=10.1002/cbic.201300430;
RA Awakawa T., Yang X.L., Wakimoto T., Abe I.;
RT "Pyranonigrin E: a PKS-NRPS hybrid metabolite from Aspergillus niger
RT identified by genome mining.";
RL ChemBioChem 14:2095-2099(2013).
RN [3]
RP FUNCTION, DISRUPTION PHENOTYPE, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=26414728; DOI=10.1021/acs.orglett.5b02435;
RA Yamamoto T., Tsunematsu Y., Noguchi H., Hotta K., Watanabe K.;
RT "Elucidation of pyranonigrin biosynthetic pathway reveals a mode of
RT tetramic acid, fused gamma-pyrone, and exo-methylene formation.";
RL Org. Lett. 17:4992-4995(2015).
CC -!- FUNCTION: Aspartic protease-like protein; part of the gene cluster that
CC mediates the biosynthesis of pyranonigrins, a family of antioxidative
CC compounds (PubMed:24106156). The first step of pyranonigrins
CC biosynthesis is performed by the hybrid PKS-NRPS synthetase that
CC condenses 6 malonyl-CoA units to an acetyl starter unit, to form a
CC 1,3,5-trioxotetradecane-6,8-dienyl-ACP (PubMed:24106156). The enoyl
CC reducrase (ER) domain of pynA is likely to be functional during the
CC first two rounds of polyketide chain extension, to generate the
CC saturated C-C bonds of the alkyl side chain (Probable). PynA
CC subsequently forms the amide bond between the acyl chain and L-serine
CC (PubMed:24106156, PubMed:26414728). Although pynA has a terminal
CC reductase domain, it appears to require the thioesterase pynI for the
CC release of the straight-chain intermediate from pynA via the formation
CC of a tetramic acid pyranonigrin J (PubMed:26414728). The
CC methyltransferase pynC then coverts pyranonigrin J to pyranonigrin I
CC via N-methylation (PubMed:26414728). The FAD-dependent monooxygenase
CC pynG catalyzes an epoxidation-mediated cyclization to form the dihydro-
CC gamma-pyrone moiety, followed by pynD-catalyzed oxidation of the
CC alcohol to the ketone and enolization to yield the characteristic
CC tetramic acid-fused gamma-pyrone core of pyranonigrin H
CC (PubMed:26414728). Pyranonigrin H is substrate of pynH for dehydration-
CC mediated exo-methylene formation from the serine side chain to produce
CC pyranonigrin E, before the oxidase pynE reduces the exo-methylene of
CC pyranonigrin E into a pendant methyl to form pyranonigrin G
CC (PubMed:26414728). The FAD-linked oxidoreductase pynB performs the
CC reverse reaction and converts pyranonigrin G back to pyranonigrin E
CC (PubMed:26414728). {ECO:0000269|PubMed:24106156,
CC ECO:0000269|PubMed:26414728, ECO:0000305|PubMed:24106156}.
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:26414728}.
CC -!- DISRUPTION PHENOTYPE: Leads to the accumulation of pyranonigrin H.
CC {ECO:0000269|PubMed:26414728}.
CC -!- SIMILARITY: Belongs to the peptidase A1 family. {ECO:0000305}.
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DR EMBL; AM270218; CAK48264.1; -; Genomic_DNA.
DR RefSeq; XP_001394035.1; XM_001393998.1.
DR AlphaFoldDB; A5ABG6; -.
DR SMR; A5ABG6; -.
DR PaxDb; A5ABG6; -.
DR EnsemblFungi; CAK48264; CAK48264; An11g00310.
DR GeneID; 4984236; -.
DR KEGG; ang:ANI_1_1540094; -.
DR VEuPathDB; FungiDB:An11g00310; -.
DR HOGENOM; CLU_039077_0_0_1; -.
DR Proteomes; UP000006706; Chromosome 7R.
DR GO; GO:0004190; F:aspartic-type endopeptidase activity; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IEA:InterPro.
DR GO; GO:0019748; P:secondary metabolic process; IGC:AspGD.
DR CDD; cd05471; pepsin_like; 1.
DR Gene3D; 2.40.70.10; -; 2.
DR InterPro; IPR001461; Aspartic_peptidase_A1.
DR InterPro; IPR034164; Pepsin-like_dom.
DR InterPro; IPR033121; PEPTIDASE_A1.
DR InterPro; IPR021109; Peptidase_aspartic_dom_sf.
DR PANTHER; PTHR47966; PTHR47966; 1.
DR Pfam; PF00026; Asp; 1.
DR SUPFAM; SSF50630; SSF50630; 1.
DR PROSITE; PS51767; PEPTIDASE_A1; 1.
PE 1: Evidence at protein level;
KW Disulfide bond; Glycoprotein; Hydrolase; Reference proteome; Signal.
FT SIGNAL 1..19
FT /evidence="ECO:0000255"
FT CHAIN 20..414
FT /note="Aspartic protease-like protein pynH"
FT /id="PRO_5002679118"
FT DOMAIN 43..410
FT /note="Peptidase A1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
FT CARBOHYD 93
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 102
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 140
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 151
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 173
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 202
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 221
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 258
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 272
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 335
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 366
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT DISULFID 333..371
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01103"
SQ SEQUENCE 414 AA; 45782 MW; 4FAD0C077CAA5384 CRC64;
MFPCSRIWSL LVAAATASAV PTSLATTHLQ SVDLLLTRSS YGFLTDIALG TPGQSLPYLV
DWTWTGHYVV TTLCYNDPTA TYDCLNVDQK IFNQTLSSTF INQTDQYGYL YWDPNHFYFT
EPAAADVATD MLRIGPTAVN TTIQAANFVF NETISAFPFS GVYGLSPVFQ GDNRSVQASF
YQGWRSGAWH SPIVSFIYCH DNATKAVCSG YDGLQTLGGY NTSHVQGDIT WYDIIVTEAI
NTLDFVYAPA VINYWALNLT RFSIGDEEQE LNKTTTLDGK QAAVAAFDHA SYGRGAPVSV
YGYQRLVELV GAKAVTLSDP PNNGEQGFYQ FDCRNSSLLP PLRYEFAGSE RAWEIVPENY
VEVLANGTNK CTFNVRTLGD GAMVMGNFGE TFAIDKYVMF DFEKLQVGIA DFAW
