NSRB_ASPN1
ID NSRB_ASPN1 Reviewed; 1792 AA.
AC A0A2I1C3X5;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 28-FEB-2018, sequence version 1.
DT 03-AUG-2022, entry version 18.
DE RecName: Full=Atrochrysone carboxylic acid synthase nsrB {ECO:0000303|PubMed:30394754};
DE Short=ACAS nsrB {ECO:0000303|PubMed:30394754};
DE EC=2.3.1.- {ECO:0000269|PubMed:32105084};
DE AltName: Full=Neosartorin biosynthesis cluster protein B {ECO:0000303|PubMed:30394754};
DE AltName: Full=Non-reducing polyketide synthase nsrB {ECO:0000303|PubMed:30394754};
GN Name=nsrB {ECO:0000303|PubMed:30394754}; ORFNames=P174DRAFT_487776;
OS Aspergillus novofumigatus (strain IBT 16806).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Aspergillus.
OX NCBI_TaxID=1392255;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=IBT 16806;
RX PubMed=29317534; DOI=10.1073/pnas.1715954115;
RA Kjaerboelling I., Vesth T.C., Frisvad J.C., Nybo J.L., Theobald S., Kuo A.,
RA Bowyer P., Matsuda Y., Mondo S., Lyhne E.K., Kogle M.E., Clum A.,
RA Lipzen A., Salamov A., Ngan C.Y., Daum C., Chiniquy J., Barry K.,
RA LaButti K., Haridas S., Simmons B.A., Magnuson J.K., Mortensen U.H.,
RA Larsen T.O., Grigoriev I.V., Baker S.E., Andersen M.R.;
RT "Linking secondary metabolites to gene clusters through genome sequencing
RT of six diverse Aspergillus species.";
RL Proc. Natl. Acad. Sci. U.S.A. 115:E753-E761(2018).
RN [2]
RP FUNCTION, DISRUPTION PHENOTYPE, AND PATHWAY.
RX PubMed=30394754; DOI=10.1021/acs.orglett.8b03123;
RA Matsuda Y., Gotfredsen C.H., Larsen T.O.;
RT "Genetic characterization of neosartorin biosynthesis provides insight into
RT heterodimeric natural product generation.";
RL Org. Lett. 20:7197-7200(2018).
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, AND PATHWAY.
RX PubMed=32105084; DOI=10.1021/acs.orglett.0c00285;
RA Wei X., Matsuda Y.;
RT "Unraveling the fungal strategy for tetrahydroxanthone biosynthesis and
RT diversification.";
RL Org. Lett. 22:1919-1923(2020).
RN [4]
RP FUNCTION.
RX PubMed=33891392; DOI=10.1021/acs.jnatprod.1c00022;
RA Wei X., Chen X., Chen L., Yan D., Wang W.G., Matsuda Y.;
RT "Heterologous biosynthesis of tetrahydroxanthone dimers: determination of
RT key factors for selective or divergent synthesis.";
RL J. Nat. Prod. 84:1544-1549(2021).
CC -!- FUNCTION: Atrochrysone carboxylic acid synthase; part of the gene
CC cluster that mediates the biosynthesis of the tetrahydroxanthone dimer
CC neosartorin, which exhibits antibacterial activity (PubMed:30394754,
CC PubMed:32105084, PubMed:33891392). The two different monomeric units
CC appear to be synthesized by the same set of enzymes, among which the
CC Baeyer-Villiger monooxygenase nsrF is the key enzyme for the divergence
CC of the biosynthetic routes (PubMed:32105084). The pathway begins with
CC the synthesis of atrochrysone thioester by the polyketide synthase nsrB
CC (PubMed:32105084). The atrochrysone carboxyl ACP thioesterase nsrC then
CC breaks the thioester bond and releases the atrochrysone carboxylic acid
CC from AacuL (PubMed:32105084). Atrochrysone carboxylic acid is
CC decarboxylated by the decarboxylase nsrE, and oxidized by the anthrone
CC oxygenase nsrD to yield emodin (PubMed:32105084). Emodin is then
CC reduced to emodin hydroquinone by the oxidoreductase nsrR
CC (PubMed:32105084). A-ring reduction by the short chain dehydrogenase
CC nsrJ, dehydration by the scytalone dehydratase-like protein nsrI and
CC probable spontaneous re-oxidation, results in overall deoxygenation to
CC chrysophanol (PubMed:32105084). The Baeyer-Villiger monooxygenase nsrF
CC accepts chrysophanol as a substrate to insert one oxygen atom at two
CC different positions to yield the precursors of both monomric units
CC (PubMed:30394754, PubMed:32105084, PubMed:33891392). NsrF is
CC promiscuous/flexible in interacting with the 2 (non methylated and
CC methylated) aromatic rings of chrysophanol, thus diverging the
CC biosynthetic pathway at this point (PubMed:30394754, PubMed:32105084,
CC PubMed:33891392). After the hydrolysis of the lactones,
CC methylesterification by the methyltransferase nsrG yields respectively
CC moniliphenone and 2,2',6'-trihydroxy-4-methyl-6-methoxya-
CC cyldiphenylmethanone (PubMed:30394754, PubMed:32105084). The next steps
CC are the hydroxylation by the FAD-dependent monooxygenase nsrK, followed
CC by isomerization by the monooxygenase nsrQ (PubMed:32105084). The short
CC chain dehydrogenase/reductase nsrO then catalyzes the C-5 ketoreduction
CC to give the xanthone skeleton of blennolide C and 5-acetylblennolide A
CC (PubMed:32105084). The acetyltransferase nsrL has a strict substrate
CC specificity and uses only blennolide A but not blennolide C to yield 5-
CC acetylblennolide A as the single-acetylated product (PubMed:30394754).
CC In the final step of the biosynthesis, the heterodimerization of the 2
CC xanthones, blennolide C and 5-acetylblennolide A, is catalyzed by the
CC cytochrome P450 monooxygenase nsrP (PubMed:30394754). NsrP can utilize
CC at least three different xanthones as its substrates to perform the
CC dimerization reaction (PubMed:30394754). {ECO:0000269|PubMed:30394754,
CC ECO:0000269|PubMed:32105084, ECO:0000269|PubMed:33891392}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=8 H(+) + holo-[ACP] + 8 malonyl-CoA = atrochrysone carboxyl-
CC [ACP] + 8 CO2 + 8 CoA + 2 H2O; Xref=Rhea:RHEA:64232, Rhea:RHEA-
CC COMP:9685, Rhea:RHEA-COMP:16552, ChEBI:CHEBI:15377,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57384, ChEBI:CHEBI:64479, ChEBI:CHEBI:149712;
CC Evidence={ECO:0000269|PubMed:32105084};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64233;
CC Evidence={ECO:0000269|PubMed:32105084};
CC -!- PATHWAY: Secondary metabolite biosynthesis.
CC {ECO:0000269|PubMed:30394754, ECO:0000269|PubMed:32105084}.
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. {ECO:0000250|UniProtKB:Q5B0D0}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of neosartorin.
CC {ECO:0000269|PubMed:30394754}.
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DR EMBL; MSZS01000005; PKX92308.1; -; Genomic_DNA.
DR SMR; A0A2I1C3X5; -.
DR VEuPathDB; FungiDB:P174DRAFT_487776; -.
DR OrthoDB; 68112at2759; -.
DR Proteomes; UP000234474; Unassembled WGS sequence.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IEA:InterPro.
DR GO; GO:0031177; F:phosphopantetheine binding; IEA:InterPro.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IEA:InterPro.
DR Gene3D; 1.10.1200.10; -; 1.
DR Gene3D; 3.10.129.110; -; 1.
DR Gene3D; 3.40.366.10; -; 2.
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; 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; IPR020841; PKS_Beta-ketoAc_synthase_dom.
DR InterPro; IPR020807; PKS_dehydratase.
DR InterPro; IPR042104; PKS_dehydratase_sf.
DR InterPro; IPR020806; PKS_PP-bd.
DR InterPro; IPR009081; PP-bd_ACP.
DR InterPro; IPR030918; PT_fungal_PKS.
DR InterPro; IPR032088; SAT.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF00698; Acyl_transf_1; 1.
DR Pfam; PF00109; ketoacyl-synt; 1.
DR Pfam; PF02801; Ketoacyl-synt_C; 1.
DR Pfam; PF00550; PP-binding; 1.
DR Pfam; PF14765; PS-DH; 1.
DR Pfam; PF16073; SAT; 1.
DR SMART; SM00827; PKS_AT; 1.
DR SMART; SM00825; PKS_KS; 1.
DR SMART; SM00823; PKS_PP; 1.
DR SUPFAM; SSF47336; SSF47336; 1.
DR SUPFAM; SSF52151; SSF52151; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR SUPFAM; SSF55048; SSF55048; 1.
DR TIGRFAMs; TIGR04532; PT_fungal_PKS; 1.
DR PROSITE; PS00606; B_KETOACYL_SYNTHASE; 1.
DR PROSITE; PS50075; CARRIER; 1.
PE 1: Evidence at protein level;
KW Multifunctional enzyme; Phosphopantetheine; Phosphoprotein;
KW Reference proteome; Transferase.
FT CHAIN 1..1792
FT /note="Atrochrysone carboxylic acid synthase nsrB"
FT /id="PRO_0000453429"
FT DOMAIN 1714..1791
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 44..284
FT /note="N-terminal acylcarrier protein transacylase domain
FT (SAT)"
FT /evidence="ECO:0000255"
FT REGION 423..837
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 937..1256
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 1326..1651
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000255"
FT REGION 1658..1715
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1663..1682
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1685..1699
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 593
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 1751
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1792 AA; 194822 MW; 034EEDE392613CBF CRC64;
MDWTTETPNT EPSLVTATPS TTESLVDPAK MKVGYFGNEF PHDDLHDLSR RLYNWSKDRQ
HTLLATFINE ATAAVRQEVR LLPATLRTLI PPFETIFSLV SHADLRHGPL GGCIDGMLLC
AVQLATFIGY YEDSTEDTFH WHNADACLAG LGTGLLSTVA VSVSPTLADM PVTGAEVVRM
AFRLGILVHE VSRILQAPTS DGGPGDSWAY VVPDAVADDV QSELDAFHDA KKTPESSKVF
ISALSRTSVT ISGPPTRLKD LFLVSDYFRD RRFVPLPVYG GLCHASHVYT KEHVDSIVNT
ESSSLVSLDS RLAPRVPIFA TSNGKPYSAK TVSGLFRNIV EELLTQRIEW DNVIEGVIQH
AKCTAVSEAL VLTFRTSLPA RDLVEALNSE SLPFKGRTQD LVPWVTKPQA EPRGPRGAQQ
AKIAIVGMSC RLPGGADDTG KFWEILNQGL DVHKKVPADR FDVETHCDPS GERLNTSLTP
YGCFIDEPGL FDAPFFNMSP REAVQTDPMQ RLAIVTAYEA LERAGYVANR TASTKLHRIG
TFYGQASDDY REVNTAQEIG TYFITGGCRA FGPGRINYFF KFSGPSYSID TACSSGLATI
HVACNSLWNG DTDMAVAGGM NVLTNSDAFA GLSKGHFLSK TPNACKTWDC EADGYCRADG
VATVIMKRLE DAEADNDNIL GVILAAGTNH SANAVSITHP HAGHQADLTR EILSKAAIDP
LDVSYVEMHG TGTQAGDAQE IQSVVDVFAP LSSTKRRATK QPLYIGAVKA NVGHGEAVAG
STALLKVLLM LQKKTIPPHV GIKNAINPGF PKDLDKRNLH IAYHRGNTSI VLEEGPVRSI
QDSDKDTRPM HVVAVSAKSK VSLKGNLQRL IHYLEANPDV SLTHLGYTTT ARRHHHNHRI
AVSTSAVPHL VRQLNSHLQS ADTHKPIPST GAPPVVFVFT GQGAAHRSMN LELFRDSPCF
RSQMLYLDSL CQSQGFPSII PAVDGSYPQD HTHPPTVTQL ALVCIELALV AYWESLGVRP
EVVVGHSLGE YAALHVAGVL SAADTIYLVG QRARMLERKC QIGSHKMLAV RAALDEVQSK
ANGKPFEVAC LNGPKDTVLS GTVSEMEALA EELEQSGLKC YHLDVAFAFH SAQTDPILQE
LEETAQTGVL FQPPRLPIIS PLLAKVIFDE KTVNAKYICR ATRETVNFVA AVEKALAMST
VDETMVWIEI GPHPVCVGFV RSIMSTVNMT VPSFRRGENN WQTLSQSLAA VHAAGVEVDW
NEFHRPFEHG LRLLDIPTYA WNNKTYWHQY NGDWALTKGN NFYDSKKKSA AAGSPLAAAP
VSSLRTSLVH RVIEESFSGT AGKVIVQSDM MQADFLAAAW GHQMNGAGVV TSSIHADIAW
TLGKYLLDSL KPNSRKSVVD MEISNLVVRE GLVAQKNRSV PQLIQVSIST ADVDSGVAYL
EWHNVTNDGV SLADQEPIVT AQIRYGTAGD YLSSWVPALH LVQGRIEALS QLADDGIANR
LSNSMAYLLF ADRLVDYADR YRGMQSVVLH GLEAFADVKT KPDDEGGVWT VPPFFIDSVC
HLAGFVMNVS DAIDTKNNFC VTPGWGSLRM ARPLVAGGRY RSYVKMIPTA EDPTVYLGDV
YVLEGDEIIG VMQGMKFRRY PRVLLNRFFT PADIKNPASG SMSCAKGARS SAQSTKSPAN
VAESVPTPAP APVPAPEPVP VQRNKQDTAA PPVAASDSTA AKALDLVAAE AAIELSDLQD
DVSFASLGVD SLMSLVIAEK LRQQLGITVS GSLFLEYPTV RDLRVWLDEY YS
