Protein: Non-reducing polyketide synthase vrtA (EC 2.3.1.-) (Viridicatumtoxin synthesis protein A) (D7PHZ2)
Organism: Penicillium aethiopicum
Function: Non-reducing polyketide synthase; part of the gene cluster that mediates the biosynthesis of viridicatumtoxin, a tetracycline-like fungal meroterpenoid with a unique, fused spirobicyclic ring system. The first step of the pathway is the production of the malonamoyl-CoA starter unit for the polyketide synthase vrtA. The aldolase vrtJ may be involved in the synthesis of the malonamate substrate for malonamoyl-CoA synthetase vrtB. The polyketide synthase vrtA then may utilize the malonamoyl-CoA starter unit, followed by sequential condensation of eight malonyl-CoA units to form the polyketide backbone. The cyclization of the last ring could be mediated by the lactamase-like protein vrtG. The proposed post-PKS tailoring steps are an hydroxylation at C5 catalyzed the cytochrome P450 monooxygenase vrtE, a hydroxylation at C12a catalyzed by VrtH and/or VrtI, and an O-methylation by the O-methyltransferase vrtF. VrtC is then proposed to catalyze the transfer of a geranyl group synthesized by vrtD to the aromatic C ring of the tetracyclic polyketide intermediate of viridicatumtoxin to yield previridicatumtoxin. Finally, the cytochrome P450 monooxygenase vrtK catalyzes the spirocyclization of the geranyl moiety of previridicatumtoxin to afford viridicatumtoxin.
Interaction partners:
Sequence:
MLHPTEVEKFPPTLLYFGNEFPNDDVNELFRRLQQHSKDRRFRLLNAYLEESILVLQDEVAKLPHHIKSRVPYFDNIVTLSEHGYLRDLGLGAAMESAFLLILQLGLFIGNHEAVDRELNLPKNVTTVAGLSVGLFSAAAIALSASLAEVVRNGAECLRVSFRLGVYAGDFSSSLEAPQPEGMLASWAHVVTGMTEESVQSELTRVNEDLGNPETSKVFISAADKSSVSVSGPPSRIKAAFLQSSDLRYSKSLPLPVYDGLCHATHIYSQDDVNTVLEISESLIPATRPFQLSVISSRTGVPFTATTASDLLSEIATELVMGTIYLDNIIEGIVRHIGAFPGAQSCRIDSFRTSIIFKGILEAIATDHPDLTIEKNDLVDWVHQDFGTRRRNDPANSKLAIVGMACRMPGGANNVEEFWQLLEQGRDACTTVPPDRFDLETHYDPTGKTENAAQTPYGNFIDRPGYFDAAFFAMSPKEAEQTDPMQRLAIVTAYEAMEMAGLVIGRTQSTRRDRIGSYYGQASDDWRELNASQNIGTYAVPGGVRGFTVGRINYFFKLSGPCLCIDTACSSSMAAVHAACTALWAGDVDVALAGGVNIITDPDNYAGLGNAHFLSPTGQCKVWDKGADGYCRAEGIGSVVIKRLEDAEADNDNILAVVLSAATNHCADAISITHPHAGHQKDNCRRVLRKAGVSPMQVSYVEMHGTGTQAGDAIESESVLDVFAPLKPLRRPDQRLHLGAVKSNIGHGEAAAGISSLIKMLLMFQKNAIPPHIGIRTEMNPQLPKDLGRRNAGLVFETTPWLRPEGKKRISVVNSFGAHGGNTTLLLEDAPERHRQRISPESTDGRSVYAISVSAKSKKSLQGNLSSLLGYLEQHPDTDLADLSYTTCARRTHHNLRVATVVSSVSALQKFLRSAIDSNIATTVQSVPSNIPSVVFTFTGQGASDRGVRQELFDDFPAFRTQVLQLDQLVQRLGFPSVVPALRGSTDEEVLSPVVSQLSIVVLEIALSRFWRLLGIRPSAVIGHSLGEYAALEVAGVLSAADVLYLVGRRAQITEQRCTPYGHSMLSVLATPDEIDRVVRRVPETSNVEYEVSCQNTHEDTVLGGAKADIEAIRKVLETTSYKCVPLAIPFAYHTSQMDVVVDELEEIAKNIPFKAPSIPVLSTMLGTVVFDGKTINPTYLRRQTRGTVKFVAAVETARDLGLIDEKTVWVDLGPHPVCVGFIRKLSPESRIAASCRRNEENLSTITKSLVTLHLAGATPLWNEFFRPNEQVYRLLNLPKYSWNETNYWIPYLGTWALDKALLKYGITPVGAKAPATLPAAGLRTSTIHQTTLETIDSMTATLHVLSDMQAPEFRAAVYGHTMNNCGVATSSIWTDMALAVGEYLYRKLVPQAKEVHMNVCDLEVLHAQVISKVKGCSQPLALEAHLDLDMQYMSLKWYNTNAATGERAPEWFASAAVRFENPDAWTAEWNRTGHLVLGRIETLRRLAADGVANRISKRLAYTLFKNVVDYSDWYRGIDDVIMNDYEAVANVTLIPDRHGTWHTPPHWIDSVCHLAGLIMNGSDASNTQDFFYVTPGSDSFRLLKPLAPGAKYISYVRMFPLSAEAGNMYAGDVYILKDDVIVGVLCQIRFRRVPRLLMDRFFSPPTADNAGVHGTPGSQRSQAPPAATHAATKSPQKTLQVPSGHVPNKASIVDTNHVQASHPSAVPVRHDQSNGVSGVSDSDSSTSITSSNSTADTSTTPTESEDADSGLVGQCIKIISRETNLDMSELTPDATFAQLGVDSLMSLVLSEKFRNELGIDVKSSLFLECPTIGEVKEWIDQNC