NSRL_ASPN1
ID NSRL_ASPN1 Reviewed; 487 AA.
AC A0A2I1C3W6;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 28-FEB-2018, sequence version 1.
DT 03-AUG-2022, entry version 13.
DE RecName: Full=Acetyltransferase nsrL {ECO:0000303|PubMed:30394754};
DE EC=2.3.1.- {ECO:0000305|PubMed:30394754};
DE AltName: Full=Neosartorin biosynthesis cluster protein L {ECO:0000303|PubMed:30394754};
GN Name=nsrL {ECO:0000303|PubMed:30394754}; ORFNames=P174DRAFT_512929;
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, 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: Acetyltransferase; part of the gene cluster that mediates the
CC biosynthesis of the tetrahydroxanthone dimer neosartorin, which
CC exhibits antibacterial activity (PubMed:30394754, PubMed:32105084,
CC PubMed:33891392). The two different monomeric units appear to be
CC synthesized by the same set of enzymes, among which the Baeyer-Villiger
CC monooxygenase nsrF is the key enzyme for the divergence of the
CC biosynthetic routes (PubMed:32105084). The pathway begins with the
CC 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 -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:30394754}.
CC -!- SUBUNIT: Monomer. {ECO:0000250|UniProtKB:Q70PR7}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of neosartorin and
CC accumulates deacetylneosartorin and novofumigatin A.
CC {ECO:0000269|PubMed:30394754}.
CC -!- SIMILARITY: Belongs to the plant acyltransferase family. {ECO:0000305}.
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DR EMBL; MSZS01000005; PKX92298.1; -; Genomic_DNA.
DR SMR; A0A2I1C3W6; -.
DR VEuPathDB; FungiDB:P174DRAFT_512929; -.
DR OrthoDB; 643224at2759; -.
DR UniPathway; UPA00213; -.
DR Proteomes; UP000234474; Unassembled WGS sequence.
DR GO; GO:0016746; F:acyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0016114; P:terpenoid biosynthetic process; IEA:UniProtKB-UniPathway.
DR Gene3D; 3.30.559.10; -; 2.
DR InterPro; IPR023213; CAT-like_dom_sf.
PE 3: Inferred from homology;
KW Acyltransferase; Reference proteome; Transferase.
FT CHAIN 1..487
FT /note="Acetyltransferase nsrL"
FT /id="PRO_0000453497"
FT ACT_SITE 174
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q70PR7"
FT ACT_SITE 418
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:Q70PR7"
SQ SEQUENCE 487 AA; 54648 MW; 981D291F0A4EFB7E CRC64;
MFNLFKQTKV APRVVAGDEV VELPFFDDTL LLQTFVLHSM FVFDQALDVL KLQDALERLG
QRAGWRKLAA RLRRNAAGQL EFHIPTEFSS QRPAIAQTHI HHETPLSQHP VSAFLPKPSA
QPAIVGNAED LRPLYEGLNC PTKLDDYLYE DRSVVGLHVV SFHDATVLTL NWIHAAFDAT
AKKAILDAWN LVMLGREDQI PTPVSYREDA LKDLGTNPLS PHALADRKTS TLGMIRWALS
NVTDLFFRSQ ETRIICVPAG FVENLHAVAM KELVSFPPGP GEERPFVSEG DILTAWVARL
AVSHLSQYPD RTVAIQNAFS ARKVLRQYLP ADQPYIANCA FFFNVLVPVK DVLGRPLSYT
AWQIRRAIKQ QTTAEQTEAY CALLRSSGQS KLPPFFGDSS MHMLSFSNWT KIDFFGLDFS
AAALKGAGPV RPKYIQNVQT PYKFTEMFPI VGKDEQGNYW LSGTRTTQNW DIIEQALREE
SPMTGST
