VRTA_PENAE
ID VRTA_PENAE Reviewed; 1824 AA.
AC D7PHZ2;
DT 06-JUL-2016, integrated into UniProtKB/Swiss-Prot.
DT 10-AUG-2010, sequence version 1.
DT 03-AUG-2022, entry version 47.
DE RecName: Full=Non-reducing polyketide synthase vrtA {ECO:0000303|PubMed:20534346};
DE EC=2.3.1.- {ECO:0000305|PubMed:20534346};
DE AltName: Full=Viridicatumtoxin synthesis protein A {ECO:0000303|PubMed:20534346};
GN Name=vrtA {ECO:0000303|PubMed:20534346};
OS Penicillium aethiopicum.
OC Eukaryota; Fungi; Dikarya; Ascomycota; Pezizomycotina; Eurotiomycetes;
OC Eurotiomycetidae; Eurotiales; Aspergillaceae; Penicillium.
OX NCBI_TaxID=36650;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=IBT 5753;
RX PubMed=20534346; DOI=10.1016/j.chembiol.2010.03.015;
RA Chooi Y.H., Cacho R., Tang Y.;
RT "Identification of the viridicatumtoxin and griseofulvin gene clusters from
RT Penicillium aethiopicum.";
RL Chem. Biol. 17:483-494(2010).
RN [2]
RP BIOTECHNOLOGY.
RX PubMed=19168978; DOI=10.1038/ja.2008.84;
RA Zheng C.J., Yu H.E., Kim E.H., Kim W.G.;
RT "Viridicatumtoxin B, a new anti-MRSA agent from Penicillium sp. FR11.";
RL J. Antibiot. 61:633-637(2008).
RN [3]
RP FUNCTION.
RX PubMed=24161266; DOI=10.1021/ja408966t;
RA Chooi Y.H., Hong Y.J., Cacho R.A., Tantillo D.J., Tang Y.;
RT "A cytochrome P450 serves as an unexpected terpene cyclase during fungal
RT meroterpenoid biosynthesis.";
RL J. Am. Chem. Soc. 135:16805-16808(2013).
RN [4]
RP BIOTECHNOLOGY.
RX PubMed=27049441; DOI=10.1038/ja.2016.35;
RA Inokoshi J., Nakamura Y., Komada S., Komatsu K., Umeyama H., Tomoda H.;
RT "Inhibition of bacterial undecaprenyl pyrophosphate synthase by small
RT fungal molecules.";
RL J. Antibiot. 69:798-805(2016).
CC -!- FUNCTION: Non-reducing polyketide synthase; part of the gene cluster
CC that mediates the biosynthesis of viridicatumtoxin, a tetracycline-like
CC fungal meroterpenoid with a unique, fused spirobicyclic ring system
CC (PubMed:20534346). The first step of the pathway is the production of
CC the malonamoyl-CoA starter unit for the polyketide synthase vrtA
CC (PubMed:20534346). The aldolase vrtJ may be involved in the synthesis
CC of the malonamate substrate for malonamoyl-CoA synthetase vrtB
CC (PubMed:20534346). The polyketide synthase vrtA then may utilize the
CC malonamoyl-CoA starter unit, followed by sequential condensation of
CC eight malonyl-CoA units to form the polyketide backbone
CC (PubMed:20534346). The cyclization of the last ring could be mediated
CC by the lactamase-like protein vrtG (PubMed:20534346). The proposed
CC post-PKS tailoring steps are an hydroxylation at C5 catalyzed the
CC cytochrome P450 monooxygenase vrtE, a hydroxylation at C12a catalyzed
CC by VrtH and/or VrtI, and an O-methylation by the O-methyltransferase
CC vrtF (PubMed:20534346, PubMed:24161266). VrtC is then proposed to
CC catalyze the transfer of a geranyl group synthesized by vrtD to the
CC aromatic C ring of the tetracyclic polyketide intermediate of
CC viridicatumtoxin to yield previridicatumtoxin (PubMed:20534346).
CC Finally, the cytochrome P450 monooxygenase vrtK catalyzes the
CC spirocyclization of the geranyl moiety of previridicatumtoxin to afford
CC viridicatumtoxin (PubMed:24161266). {ECO:0000269|PubMed:20534346,
CC ECO:0000269|PubMed:24161266}.
CC -!- PATHWAY: Secondary metabolite biosynthesis; terpenoid biosynthesis.
CC {ECO:0000269|PubMed:20534346}.
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 (By similarity).
CC {ECO:0000250|UniProtKB:Q5B0D0}.
CC -!- DISRUPTION PHENOTYPE: Impairs the production of viridicatumtoxin
CC (PubMed:20534346). {ECO:0000269|PubMed:20534346}.
CC -!- BIOTECHNOLOGY: Viridicatumtoxin and its derivative, viridicatumtoxin B,
CC exhibit anti-methicillin-resistant Staphylococcus aureus (anti-MRSA)
CC activity (PubMed:19168978). Moreover, viridicatumtoxin and a C2 acetyl
CC analog, spirohexaline, have been demonstrated to inhibit bacterial
CC undecaprenyl diphosphate synthase, a potential new target for
CC antibiotic development (PubMed:27049441). {ECO:0000269|PubMed:19168978,
CC ECO:0000269|PubMed:27049441}.
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DR EMBL; GU574477; ADI24926.1; -; Genomic_DNA.
DR AlphaFoldDB; D7PHZ2; -.
DR SMR; D7PHZ2; -.
DR PRIDE; D7PHZ2; -.
DR BioCyc; MetaCyc:MON-19274; -.
DR UniPathway; UPA00213; -.
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 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; -; 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; IPR020841; PKS_Beta-ketoAc_synthase_dom.
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; 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 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; Transferase.
FT CHAIN 1..1824
FT /note="Non-reducing polyketide synthase vrtA"
FT /id="PRO_0000436828"
FT DOMAIN 1747..1824
FT /note="Carrier"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
FT REGION 5..400
FT /note="N-terminal acylcarrier protein transacylase domain
FT (SAT)"
FT /evidence="ECO:0000255"
FT REGION 396..771
FT /note="Ketosynthase (KS) domain"
FT /evidence="ECO:0000255"
FT REGION 935..1259
FT /note="Malonyl-CoA:ACP transacylase (MAT) domain"
FT /evidence="ECO:0000255"
FT REGION 1325..1644
FT /note="Product template (PT) domain"
FT /evidence="ECO:0000250|UniProtKB:Q5B0D0, ECO:0000255"
FT REGION 1649..1690
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1702..1750
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1653..1690
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1702..1748
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 569
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10022"
FT MOD_RES 1784
FT /note="O-(pantetheine 4'-phosphoryl)serine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00258"
SQ SEQUENCE 1824 AA; 199420 MW; FC9A33E0FD47BC71 CRC64;
MLHPTEVEKF PPTLLYFGNE FPNDDVNELF RRLQQHSKDR RFRLLNAYLE ESILVLQDEV
AKLPHHIKSR VPYFDNIVTL SEHGYLRDLG LGAAMESAFL LILQLGLFIG NHEAVDRELN
LPKNVTTVAG LSVGLFSAAA IALSASLAEV VRNGAECLRV SFRLGVYAGD FSSSLEAPQP
EGMLASWAHV VTGMTEESVQ SELTRVNEDL GNPETSKVFI SAADKSSVSV SGPPSRIKAA
FLQSSDLRYS KSLPLPVYDG LCHATHIYSQ DDVNTVLEIS ESLIPATRPF QLSVISSRTG
VPFTATTASD LLSEIATELV MGTIYLDNII EGIVRHIGAF PGAQSCRIDS FRTSIIFKGI
LEAIATDHPD LTIEKNDLVD WVHQDFGTRR RNDPANSKLA IVGMACRMPG GANNVEEFWQ
LLEQGRDACT TVPPDRFDLE THYDPTGKTE NAAQTPYGNF IDRPGYFDAA FFAMSPKEAE
QTDPMQRLAI VTAYEAMEMA GLVIGRTQST RRDRIGSYYG QASDDWRELN ASQNIGTYAV
PGGVRGFTVG RINYFFKLSG PCLCIDTACS SSMAAVHAAC TALWAGDVDV ALAGGVNIIT
DPDNYAGLGN AHFLSPTGQC KVWDKGADGY CRAEGIGSVV IKRLEDAEAD NDNILAVVLS
AATNHCADAI SITHPHAGHQ KDNCRRVLRK AGVSPMQVSY VEMHGTGTQA GDAIESESVL
DVFAPLKPLR RPDQRLHLGA VKSNIGHGEA AAGISSLIKM LLMFQKNAIP PHIGIRTEMN
PQLPKDLGRR NAGLVFETTP WLRPEGKKRI SVVNSFGAHG GNTTLLLEDA PERHRQRISP
ESTDGRSVYA ISVSAKSKKS LQGNLSSLLG YLEQHPDTDL ADLSYTTCAR RTHHNLRVAT
VVSSVSALQK FLRSAIDSNI ATTVQSVPSN IPSVVFTFTG QGASDRGVRQ ELFDDFPAFR
TQVLQLDQLV QRLGFPSVVP ALRGSTDEEV LSPVVSQLSI VVLEIALSRF WRLLGIRPSA
VIGHSLGEYA ALEVAGVLSA ADVLYLVGRR AQITEQRCTP YGHSMLSVLA TPDEIDRVVR
RVPETSNVEY EVSCQNTHED TVLGGAKADI EAIRKVLETT SYKCVPLAIP FAYHTSQMDV
VVDELEEIAK NIPFKAPSIP VLSTMLGTVV FDGKTINPTY LRRQTRGTVK FVAAVETARD
LGLIDEKTVW VDLGPHPVCV GFIRKLSPES RIAASCRRNE ENLSTITKSL VTLHLAGATP
LWNEFFRPNE QVYRLLNLPK YSWNETNYWI PYLGTWALDK ALLKYGITPV GAKAPATLPA
AGLRTSTIHQ TTLETIDSMT ATLHVLSDMQ APEFRAAVYG HTMNNCGVAT SSIWTDMALA
VGEYLYRKLV PQAKEVHMNV CDLEVLHAQV ISKVKGCSQP LALEAHLDLD MQYMSLKWYN
TNAATGERAP EWFASAAVRF ENPDAWTAEW NRTGHLVLGR IETLRRLAAD GVANRISKRL
AYTLFKNVVD YSDWYRGIDD VIMNDYEAVA NVTLIPDRHG TWHTPPHWID SVCHLAGLIM
NGSDASNTQD FFYVTPGSDS FRLLKPLAPG AKYISYVRMF PLSAEAGNMY AGDVYILKDD
VIVGVLCQIR FRRVPRLLMD RFFSPPTADN AGVHGTPGSQ RSQAPPAATH AATKSPQKTL
QVPSGHVPNK ASIVDTNHVQ ASHPSAVPVR HDQSNGVSGV SDSDSSTSIT SSNSTADTST
TPTESEDADS GLVGQCIKII SRETNLDMSE LTPDATFAQL GVDSLMSLVL SEKFRNELGI
DVKSSLFLEC PTIGEVKEWI DQNC
