Protein: Non-reducing polyketide synthase VdtA (A0A443HK81)
Organism: Byssochlamys spectabilis (Paecilomyces variotii)
Function: Non-reducing polyketide synthase; part of the gene cluster that mediates the biosynthesis of viriditoxin, one of the 'classical' secondary metabolites produced by fungi and that has antibacterial activity. The first step is performed by the polyketide synthase VdtA which condenses one acetyl- CoA and 6 malonyl-CoA units to form the heptaketide monomer backbone of viriditoxin. The product of VdtA is then O-methylated on C7 by the O-methyltransferase VdtC. The O-methyl group is important for the stereoselective coupling of the monomers at the final step of viriditoxin biosynthesis. The short- chain dehydrogenase/reductase VdtF then acts as a stereospecific reductase converting the pyrone to dihydropyrone via the reduction of the C3-C4 double bond. The FAD- binding monooxygenase VdtE then converts the ketone group into a methyl-ester group to yield semi-viriditoxin. Finally, the laccase VdtB is involved in dimerization of 2 semi-viriditoxin molecules to yield the final viriditoxin. VdtB is responsible for the regioselective 6,6'-coupling of semi-viriditoxin, which yields (M)- viriditoxin and (P)-viriditoxin at a ratio of 1:2. The non-catalytic carboxylesterase-like protein VdtD affects the stereochemistical outcome of the coupling. The highly reducing polyketide synthase VdtX is not involved in viriditoxin synthesis, but might possibly play a role in the production of additional metabolites not identified yet
Subcellular location: Cytoplasmic vesicle. Note=The vesicles where VdtA is targeted remain unknown
Sequence: MAQKLRFYLFGDQTYDYDEQLRALLTSHDPVVRSFLERAYYTLRAEVARIPNGYQARISRFSSIAELLSQRREHGVDASLEQALTVVYQLASFMRLHSERSLSYPSADDAHCLGLCTGALSAAAVSSSRSLSELLPAAIETVILAFRTGLHASDSGRRIEESSAAAKCWSISLQGLEGHVARKLLEEWSNKKRLPPMSRPYISAYASGGVTISGPPSVLAELRNTPGLSKLRAKDIPIHAPYHSSAIFNQCDVETILSSALIDLASRATHVPILSTGTGRLVWAGTLPAAIQSALQDVLLRPISWENMSCGISTCLQSIDPSEVEVIPIATLAGPLLCRSVQVAKSQIPATIDPKNDVMNEAQSQIAEAMDRAKIAIVGMSGRFPGAENVDSLWELLMAGRDMCKEVPPTRWNVDTHVDPTGKRKNTSKIRWGCWLDNPDMFDARFFNMSPREAPQVDPAQRIALITAYEAIEQAGIVPGRTPSTQEDRVGVFFGTTSNDWCESNSGQDIDTYYIPGANRAFIPGRINYVFKFSGPSYSIDTACSSSLSALHVACNALWHGDIDTAIAGGTNVLTNPDMTAGLDRGHFLSATGNCKTFDDTADGYCRGEGVATVVLKRMDDAIADKDPILGVIRGVYTNHSAEAESITRPHVGAQKAIFQHVLNHSGIRPQDISYIEMHGTGTQAGDMREMTSVLDTFSPQYPGAIQREKPLYLGAVKSNIGHGESVSGVTALVKVIMMMQNNTIPPHRGVHTRLNRRFPSNLDERNVHIAFQATEWPRGQTPRRAFINNFSAAGGNSSVLVEDPPLILKEEGADPRSSHVIAVSAKSPSALRKNLESMRRYAMSEHTEKSLCELSYTTTARRIHHSHRLMFAGSSLEDILREMESKLAIKEPFSPCAPLQSVIFTFTGQGAQYPGMGQVFFNNFSVFRSDLCRLDDLAQKLGFPTFLPIFSASTHARLEGFTPTVVQLANTCMQLALTRLWVSWGIRPSAVVGHSIGEYAALNTAGVLSDADTVYLVGKRAQLLEEKCNRGSHTMLAALASFEKVSRLLDSAPCEVACINGPEEIVLAGPRSHMTDIQKILVAHSIRCTMLQVPFAFHSSQVDPILQDFQSAIEGVTFHKPTIPVISPLLGDFVTETGTFNPNYLARHCREPVNILQALRQASTMNLVHDSSVVMEFGPHPVVSGMVKSTLGNSIKALPTLQRNRNTWEVLTESVSTLYCMGFDINWTEYHRDFPSSQRVLRLPSYSWDLKSYWIPYRNDWTLYKGDIVPESSIALPTHQNKPHSTSPKQQAPTPILETTTLHRIVDEKSTEGTFSITCESDVSRPDLSPLVQGHKVEGIGLCTPSVYADIGFTLGNYLLDRFPTRFGPDTKVVDVTDMVIEKALMPLNAGPQLLRVTASLIWSEKEASVRFYSVDENHTETVQHSHCRIKFSDRSTYQAYQEQISAVKARMFEMKTNSSSGRTYRFNGPMAYNMVQALAEFHPDYRCIDETILDNETLEAACTVSFGNVKKEGVFHTHPGYIDGLTQSGGFVMNANDKTNLGVEVFVNHGWDSFQLYEPVTDDRSYQTHVRMRPAESNQWKGDVVVLSGENLVACVRGLTIQGVPRRVLRYILQSSAKTTQTATSSVPAPSQAPVMVPQIVQVPKAKPISQISGTLTEALRIICEQSGVPLAELTDDATFANIGVDSLLALTITSAFVEELDLDVDSSLFMDYPTVADLKRFFDKINTQHAPAPAPVSDAPKQLQPSSSPVASATPSAPIHGRSKFESVLNILTEESGVEMAGLPDSTALADIGIDSLLSLVVTSRLNDELELDVSSEDFNDCLTIRDLKAHFMSKNSDNGSSAVLTPQPSRDSALPERTRPRVADTSDEEDAPVSANEFTTSARSTSKYMAVLNIISEESGMAIEDFTDNVMFADIGIDSLLSLVIGGRIREELSFDLEVDSLFVDYPDVKGLRSFFGFESNKTATNPTASQSSSSISSGTSVFDTSPSPTDLDILTPESSLSQEEFEQPLTIATKPLPPATSVTLQGLPSKAHKILFLFPDGSGSATSYAKLPRLGADVAIIGLNSPYLMDGANMTCTFDELVTLYLTEIQRRQPAGPYHLGGWSAGGILAYRAAQILQKAAANPQKPVVESLLLLDSPPPTGLGKLPKHFFDYCDQIGIFGQGTAKAPEWLITHFQGTNSVLHEYHATPFSFGTAPRTGIIWASQTVFETRAVAPPPVRPDDTEDMKFLTERRTDFSAGSWGHMFPGTEVLIETAYGADHFSLLVSLLFRD
InterPro domains: - IPR014043: Acyl transferase domain (domain) [905-1208]
- IPR032088: Starter unit:ACP transacylase, SAT domain (domain) [8-243]
- IPR036736: ACP-like superfamily (homologous_superfamily) [1656-1960]
- IPR016035: Acyl transferase/acyl hydrolase/lysophospholipase (homologous_superfamily) [8-1194]
- IPR001227: Acyl transferase domain superfamily (homologous_superfamily) [2-1209]
- IPR020841: Polyketide synthase, beta-ketoacyl synthase domain (domain) [372-807]
- IPR016039: Thiolase-like (homologous_superfamily) [369-809]
- IPR050091: Polyketide and Nonribosomal Peptide Biosynthesis Enzymes (family) [374-1572]
- IPR001031: Thioesterase (domain) [2039-2146]
- IPR049551: Polyketide synthase, dehydratase domain, C-terminal (domain) [1481-1609]
- IPR018201: Beta-ketoacyl synthase, active site (active_site) [535-551]
- IPR042104: Polyketide synthase, dehydratase domain superfamily (homologous_superfamily) [1297-1617]
- IPR030918: Polyketide product template domain (domain) [1300-1616]
- IPR014031: Beta-ketoacyl synthase, C-terminal (domain) [630-751]
- IPR016036: Malonyl-CoA ACP transacylase, ACP-binding (homologous_superfamily) [1033-1094]
- IPR009081: Phosphopantetheine binding ACP domain (domain) [1655-1964]
- IPR020806: Polyketide synthase-like, phosphopantetheine-binding domain (domain) [1658-1839]
- IPR029058: Alpha/Beta hydrolase fold (homologous_superfamily) [2016-2271]
- IPR014030: Beta-ketoacyl synthase-like, N-terminal (domain) [374-622]
- IPR049900: Polyketide synthase, dehydratase domain (domain) [1304-1612]
Interaction partners: - Alcohol dehydrogenase
- Acetyl-CoA carboxylase
- holo-[acyl-carrier-protein] synthase
- Putative thioesterase
- [acyl-carrier-protein] S-malonyltransferase
- Putative hybrid NRPS/PKS enzyme
- Carrier domain-containing protein
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding), GO:0042802 (identical protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009987 (cellular process), GO:0009058 (biosynthetic process), GO:0044237 (cellular metabolic process), GO:0019748 (secondary metabolic process), GO:0071704 (organic substance metabolic process), GO:0044281 (small molecule metabolic process), GO:0044550 (secondary metabolite biosynthetic process), GO:1901615 (organic hydroxy compound metabolic process), GO:0044249 (cellular biosynthetic process), GO:0009404 (toxin metabolic process), GO:1901360 (organic cyclic compound metabolic process), GO:1901576 (organic substance biosynthetic process), GO:0006725 (cellular aromatic compound metabolic process), GO:0018904 (ether metabolic process), GO:0030638 (polyketide metabolic process), GO:1901617 (organic hydroxy compound biosynthetic process), GO:1901503 (ether biosynthetic process), GO:1901362 (organic cyclic compound biosynthetic process), GO:0043385 (mycotoxin metabolic process), GO:0009403 (toxin biosynthetic process), GO:0019438 (aromatic compound biosynthetic process), GO:0030639 (polyketide biosynthetic process), GO:0018958 (phenol-containing compound metabolic process), GO:0043386 (mycotoxin biosynthetic process), GO:0046189 (phenol-containing compound biosynthetic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0032991 (protein-containing complex), GO:1902494 (catalytic complex), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005737 (cytoplasm), GO:0043229 (intracellular organelle), GO:1990204 (oxidoreductase complex), GO:0005739 (mitochondrion), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle)