6-methylsalicylic acid synthase; part of the gene cluster that mediates the biosynthesis of patulin, an acetate-derived tetraketide mycotoxin produced by several fungal species that shows antimicrobial properties against several bacteria (PubMed:30100914, PubMed:25625822, PubMed:30680886, PubMed:35339702). PatK catalyzes the first step of the pathway which is the synthesis of 6-methylsalicylic acid via condensation of 1 acetate and 3 malonate units (PubMed:30680886). The pathway begins with the synthesis of 6-methylsalicylic acid by the polyketide synthase (PKS) patK via condensation of acetate and malonate units. The 6-methylsalicylic acid decarboxylase patG then catalyzes the decarboxylation of 6-methylsalicylic acid to yield m-cresol (also known as 3-methylphenol). These first reactions occur in the cytosol. The intermediate m-cresol is then transported into the endoplasmic reticulum where the cytochrome P450 monooxygenase patH converts it to m-hydroxybenzyl alcohol, which is further converted to gentisyl alcohol by the cytochrome P450 monooxygenase patI. The oxidoreductases patJ and patO further convert gentisyl alcohol to isoepoxydon in the vacuole. PatN catalyzes then the transformation of isoepoxydon into phyllostine. The cluster protein patF is responsible for the conversion from phyllostine to neopatulin whereas the alcohol dehydrogenase patD converts neopatulin to E-ascladiol. The steps between isoepoxydon and E-ascladiol occur in the cytosol, and E-ascladiol is probably secreted to the extracellular space by one of the cluster-specific transporters patC or patM. Finally, the secreted patulin synthase patE catalyzes the conversion of E-ascladiol to patulin (PubMed:30680886) (Probable). acetyl-CoA + 3 H(+) + 3 malonyl-CoA + NADPH = 6-methylsalicylate + 3 CO2 + 4 CoA + H2O + NADP(+) Mycotoxin biosynthesis; patulin biosynthesis. Expression is correlated with the production of patulin (PubMed:25120234). Expression is positively regulated by the secondary metabolism regulator laeA (PubMed:27528575, PubMed:30100914). Expression is strongly decreased with increased sucrose concentrations. This decrease is lost in the presence of malic acid (PubMed:30100914). Expression is increased with pH changes from 2.5 to 3.5 in the presence of a limiting concentration of sucrose, 50 mM (PubMed:30100914). Natural phenols present in apple fruits such as chlorogenic acid or the flavonoid epicatechin modulate patulin biosynthesis. They increase expression in the absence of sucrose, have little impact in the presence of 15 mM sucrose, and decrease expression in 175 mM sucrose (PubMed:30100914). Expression is positively regulated by the patulin cluster-specific transcription factor patL (PubMed:25625822). Finally, expression is also positively regulated by the velvet family proteins transcription regulators veA, velB, velC, but not vosA (PubMed:30680886). Multidomain protein; including a starter unit:ACP transacylase (SAT) that selects the starter unit; a ketosynthase (KS) that catalyzes repeated decarboxylative condensation to elongate the polyketide backbone; a malonyl-CoA:ACP transacylase (MAT) that selects and transfers the extender unit malonyl-CoA; a product template (PT) domain that controls the immediate cyclization regioselectivity of the reactive polyketide backbone; and an acyl-carrier protein (ACP) that serves as the tether of the growing and completed polyketide via its phosphopantetheinyl arm. Completely abolishes the production of patulin and shows significant slower colony expansion. Patulin was originally used as an antibiotic and specifically trialed to be used against the common cold, but it is no longer used for that purpose since it has been shown to induce immunological, neurological and gastrointestinal effects (PubMed:15082620). Genotoxic effects of patulin with dose-dependent increase in DNA strand breaks in brain, liver and kidneys have been detected in mice (PubMed:22222931). However, more recently, it has been proposed that patulin might also have anti-tumor properties (PubMed:26619846).