Protein: Atrochrysone carboxylic acid synthase (ACAS) (EC 2.3.1.-) (Non-reducing polyketide synthase tpcC) (Trypacidin synthesis protein C) (Q4WQZ5)
Organism: Aspergillus fumigatus (strain ATCC MYA-4609 / CBS 101355 / FGSC A1100 / Af293) (Neosartorya fumigata)
Function: Non-reducing polyketide synthase; part of the gene cluster that mediates the biosynthesis of trypacidin, a mycotoxin with antiprotozoal activity and that plays a role in the infection process. The pathway begins with the synthesis of atrochrysone thioester by the polyketide synthase (PKS) tpcC. The atrochrysone carboxyl ACP thioesterase tpcB then breaks the thioester bond and releases the atrochrysone carboxylic acid from tpcC. The decarboxylase tpcK converts atrochrysone carboxylic acid to atrochrysone which is further reduced into emodin anthrone. The next step is performed by the emodin anthrone oxygenase tpcL that catalyzes the oxidation of emodin anthrone to emodin. Emodin O-methyltransferase encoded by tpcA catalyzes methylation of the 8-hydroxy group of emodin to form questin. Ring cleavage of questin by questin oxidase tpcI leads to desmethylsulochrin via several intermediates including questin epoxide (By similarity). Another methylation step catalyzed by tpcM leads to the formation of sulochrin which is further converted to monomethylsulfochrin by tpcH. Finally, the tpcJ catalyzes the conversion of monomethylsulfochrin to trypacidin. Trypacidin is toxic for human pulmonary and bronchial epithelial cells by initiating the intracellular formation of nitric oxide (NO) and hydrogen peroxide (H(2)O(2)), thus triggering host necrotic cell death. The trypacidin pathway is also able to produce endocrocin via a distinct route from the endocrocin Enc pathway.
Interaction partners:
- Atrochrysone carboxyl ACP thioesterase
- Oxidoreductase tpcG
- Anthrone oxygenase tpcL
- Trypacidin cluster transcriptional coactivator tpcD
- Decarboxylase tpcK
- Polyketide synthase, putative
Sequence:
MRPVDFTPSSESPTAEKGMKVVYFGNELPQDGIQGICRRLHTYTKDRRYPLLARFIEESTWAVHDEVRQLHAAQKALVSPFESVLHLAEQPELCRGPLCGSIEGVLLCVIQLGTFIGYYEDSPNEYTFDSANTYLTGLGLGLLASTAVSLSPTLADLPLAGAEVVRVAFRLGVLVADVSQNLQPADATGERDSWAYVIPNVAPKEAEEELAVIHTRENTPEASRIFISAISRTSVTISGPPARLRRLFRMSDFFRDRTFVALPVYGGLCHAKHIYNSQHARSVVQGPSIAALDTRFIARYPILSTGSGEPFPTATTATELFEHVMTEILTQAIEWENVIQGVVERAKLLSVSEVQVQVFRNSHPVHDLLSALETSLREGVEVAIKDLGPWITRTRDEERPPPRGTAQSKIAIVGMSCRMPSGATDTEKFWDILEQGLDVHRKIPPDRFDVDSHYDPAGKRVNASHTPYGCFIDEPGLFDAPFFNMSPREAQQTDPMQRLAIVTAYEALERAGYVANRTRSSNKHRMGTFYGQASDDYREVNSAQEISTYFIPGGCRAFGPGRINYFFKLWGPSFSIDTACSSSLATIQAACTALWNGDTDTVVAGGMNVLTNSDAFAGLSHGHFLTKTPNACKTWDCEADGYCRADGVASIVMKRLEDAEADNDNILGVILGAATNHSAEAISITHPHAGAQSCLSRQVLRSAGIDPMDVSYVEMHGTGTQAGDAEEIKSVSDVFAPAVKRRSSQQPVFIGAVKANVGHGEAVAGVTALVKVLLMFQKEAIPPHVGIKNSINPGFPKDLDQRNLRIPYEKKPWPRRPGRKRIAMVNNFSAAGGNSTLAIEEGPLRPKPAGAIDPRSSHLVTVSAKSKISLKGNLERLLSFLDAHPDVALSDLAYTTTARRHHHNHRVAVATSDIADLKAQLCKTLESDSVNTLQPISATGPPPIAFAFTGQGSSYKSWDLQLFQHSPYFRSQILHLDTLAQGQGFPSFVPAIDGSYPRDHAHCPVITQLALVCTEIALAKYWVSLGVTPDVVVGHSLGEYAALHIAGVLSASDAIFLVGQRACLLQERCQPSSHQMMAVRASLEQIEQFAGSLPYEIACVNGPREMVLSGTREEMAAVARLLEAEGFKCIVLEVAFAFHSAQMDPILDEFEALAASGVVFQAPNLPVISPLLSKVVFDEHTIDSVYMRRATRETVHFLSAMKMAHKISTIDDATVWVEIGPHPVCVNFVRSSLPSTSVTVPSFRRGEDNWVTLTSSLGILHCAGVPVDWNEFHQPFERALRLLDLPTYSWNEKTYWIQYQGNWALTKGNTFYDDEAPQTKALAGLASELRTSTVQQIIHEQYDGAAGSVVMQSDLMQPDFLAAAYGHKMNGRGVVTSSIHADIAFTLGEYLYKKLNPNQEPHMNIANLEVVKALVAQENTKSPQLIQVSASTDNIRSRQAHLKWHNVINGSIEEPFASATVYYEEASDWLASWRPATHLVQGRIHALEQLAEDGVANRFTRRMAYGLFASSLVDYADKYRGMQSVVLHELEAFADVVLTTEKGGTWTVPPYFIDSVAHLAGFIMNVSDANDTNANFCVTPGWSSMRFAAPLLPGSKYRSYVKMIPTVEDNNIYLGDVYILQDETIVGMVGGIKFRRYPRILLNRFFSAPDADARKSTPATSAPAPAPPAGSEALQPKAAPASTPAAPASADAPTTNGVKAAAEPDANSTAAKAIALVATEAGLGLSDLKDSASFSSLGIDSLMSLVISEKFRETLGVTVTGSLFLEYPTVGDLKSWLLEYYS