Function
6-methylsalicylic acid synthase; part of the gene cluster that mediates the biosynthesis of terreic acid, a quinone epoxide inhibitor of Bruton's tyrosine kinase (PubMed:24534845, PubMed:25265334). The first step of the pathway is the synthesis of 6-methylsalicylic acid (6-MSA) by the 6-methylsalicylic acid synthase atX (PubMed:9003280, PubMed:9438344, PubMed:25265334). In the biosynthesis of 6-MSA, atX utilizes one acetyl-CoA and three malonyl-CoAs as its substrates and catalyzes a series of programmed reactions including Claisen condensation, dehydration, reduction, and cyclization to yield 6-MSA (PubMed:9003280, PubMed:9438344, PubMed:25265334). The 6-methylsalicylic acid decarboxylase atA then catalyzes the decarboxylative hydroxylation of 6-MSA to 3-methylcatechol (PubMed:25265334). The next step is the conversion of 3-methylcatechol to terremutin via several oxidation steps involving the cytochrome P450 monooxygenase atE and probably also the cytochrome P450 monooxygenase atG (PubMed:25265334). Lastly, atC is required for the oxidation of terremutin to terreic acid (PubMed:25265334). No function could be assigned to atD yet, although it is involved in the biosynthesis of terreic acid (PubMed:25265334).
Sequence
MEVHGDEVLSVDSGVSTPPSTGSGFRRPLETPGTEIGNLNLNPQNEVAVVGMACRLAGGNNSPEELWQSILNRKDASGEIPSMRWEPYYRRDIRNPKILDQTTKRGYFLDHVENFDAAFFGVSPKEAEQMDPQQRLSLEVTWEALEDAGIPPQSLSGSETAVFMGVNSDDYSKLLLEDIPNVEAWMGIGTAYCGVPNRISYHLNLMGPSTAVDAACASSLVAIHHGRQAILQGESEVAIVGGVNALCGPGLTRVLDKAGATSTEGRCLSFDEDAKGYGRGEGAAVVILKRLSTAIRDGDHIRAIIKGSAVAQDGKTNGIMAPNAKAQELVAWNALRTAGVDPLTVGYVEAHATSTPLGDPTEVSAVSAVYGKGRPEGNPCFIGSVKPNVGHLEAGAGAVGFIKAVMAVEKAIFPPQTNLKRLNSRIDWGQAGVKVVQETLEWPGNEDDVRRAGVCSYGYGGTVSHAIIEEFAQQLQRPTTNTTDEDPLPRILLLSAPQERRLALQARTQASWIAAEGRNRTLESIATTLSTRRGHHDYRAAIIAENHDDAVQKLSDIVNGKAAEWTTSSRVLDASCSKDVVWVFSGHGAQWTAMATDLLKDIVFYQTISRLDPIVEREMGFSALHSLASGDFESSIKVQVLTYLVQVGLAAILRSKGLEPQAVIGHSVGEIAASVAAGCLTAEEGALIVTRRANLYRRVMGAGAMVLVNIPFVDMEKELQGRTDLVAAIDSSPSSCVVSGATEAVLALVEDLKSRGVNAFRVKTDIPFHHPMLDQLSEPLREAMAGSLSPRKPRVRLYSTSAEDPRSMVARDIYYWTSNMVNPVRLTAAVQAAVDDGLRLFLEVSSHPIVSHSVRETMLDLGVEDFTVTNTMARNKPADKTILSSIAQLHCRGAVVNWKKQLPGPWALDVPLTTWDHKPYWRHIHTGPISASTLHDVDKHTLLGQRVPVAGETTMVFTTQMDDQTKPFPGSHPLHGSEIVPAAALVNTFLHATGATTLSNITLRVPVAISQPRDIQVVVSQNQIKICSRLTQKAGSGADEGSWLTHTTGQWEAGGSKNAPAQLDIAAIKARLANNKLADNFSIDYLDKVGVSAMGFPWAVTEHYGTLQEMIARVDVAPDVPATSPLPWDAASWAPILDAATSVGSTLFFDQPRLRMPAHIHGVQVYTTQPPLKVGYLYVEKAGDRDLAVHVSVCDELGTVLARFESMRFSEIEGTPGSNGSEESLVHQLAWPPAIYSEKPLTINNVVLVSRDKNVADLYCGSLKDRVSSITVLDAAADLLSLSQDSSSVLQAKDTAVVYVPGPLHSADSIPTAAHSFLMELLLLVKIIVNGSLPTKVFVLTDRVCESESATALAQSPIHGVSRIIAAEHPDQWGGLIDVETPGQFPLETMKYVQEADNIRISDGIPRIARLRPLPRDKLLPPSKQTSLLPRPESTYLITGGLGALGLEVAQFLVEKGARRLILVSRRALPPRREWADILADASSSLAPALETIQALEAQGATVHTLAVDISSPDAAPQLAVAIDSLSLPPVRGVVHAAGVLDSQLVLSATSDSVERVLAPKITGALVLGTVFPPKALDFFMLFSSCGQLLGFPGQASYASGNAFLDAFATSRRHQGDNAVAVQWTSWRSLGMAASTDFINAELASKGITDITRDEGFRAWMHISKYDIDQAAVLRSLAFEADEPLPTPILTDIAVRKAGSASSADAPSAAPKETNEMPESIPERRTWLDERIRDCVARVLQLGSSDEVDSKAALSDLGVDSVMTVSLRGQLQKTLGVKVPPTLTWSCPTVSHLVGWFLEKMGN