Protein: 6-methylsalicylic acid synthase (6MSAS) (EC 2.3.1.165) (Non-reducing polyketide synthase patK) (Patulin biosynthesis cluster protein K) (A0A075TRC0)
Organism: Penicillium expansum (Blue mold rot fungus)
Function: 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. 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. 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 (Probable).
Subcellular location: Cytoplasm, cytosol {ECO:0000269|PubMed:30680886}.
Interaction partners:
- AMP-dependent synthetase/ligase
- Carrier domain-containing protein
- AMP-dependent synthetase/ligase
- AMP-dependent synthetase/ligase
- AMP-dependent synthetase/ligase
- AMP-dependent synthetase/ligase
- Tetrapyrrole biosynthesis, glutamate-1-semialdehyde aminotransferase
Sequence:
MHSVSPSTYPSGGTSPAPADTPGTEYSEYEFSNDVAVVGMACRVAGGNHNPELLWQSLLSQKSAVGEIPEMRWEPYYRRDPRNAKELKKTTSRGYFLDRLEDFDCQFFGISPKEAEQMDPQQRVSLEVASEALEDAGIPAKSLSGSDTAVFWGVNSDDYSKLVLEDLPNVEAWMGIGTAYCGVPNRISYHLNLMGPSTAVDAACASSLVAVHHGVQAIRLGESQVAIVGGVNALCGPGLTRVLDKAGAISSDGSCKSFDDDAHGYARGEGAGALVLKSLHRALLDHDNVLAVIKGSAVAQDGKTNGIMAPNAKAQQLAARTALNVAGVDPSTVRYVEAHATSTPLGDPTEISAIAGVYGTNRPADDPCYIGSIKPNIGHLEAGAGVMGFIKAILTIQKGVLPPQANLTNLNSRIDWKTAGVKVVQEATPWPSSDPIRRAGVCSYGYGGTVSHAVIEEFNPILRPDPLDDGAATGPGLLLLSGPQEKRLALQAKTLREWMTADGKDNNLSEILTTLATRRDHHDYRAALVVDDHLDATQVLQALANGTDHSFTTQSRVLGADVSKDVVWVFSGHGAQWPDMGKQLIHNPVFFAAIQPLDELIQAEIGLSPIELLRTGDFESSDRVQILTYLMQIGLSAILQSNGITPQAVIGHSVGEIAASVVAGALTSAEGALIVTRRALLYRQVMGKGGMILVNLPSAETEEILGRRQDLVVAIDSSPSSCVVAGDKDIVAETAEAFKARGVKTFTVKSDIAFHSPTLNVLMDPLRDALGQALAPTVHIKLYSTALVDPRGQDVRDLEYWTGNMVNRVRLTSAIQAAVEDGYRLFLEVSTHPVVSHSINETLMDAGLEDFAVIPTLLRKKPTEKHILHSIAQLHCRGAEVNWAAQMPGRWATGLPTTTWMHKPIWRKIETAPLHTGLTHDVEKHTLLGQRIPVPGTDTFVYTSRLDNETKPFPGSHPLHGTEIVPAAGLINTFLKGTGGQMLQNVVLRVPVAINAPRSVQVVVQQDQVKVVSRLISSDPSLSDDDASWVTHTTAYWDRKVLGSADRIDLAAVKARLTTKLADNFSIDYLDKVGVSAMGFPWAVTEHYRDTKQMLARVDVNPAVLGDDPLPWDSSSWAPVLDAATSVGSTVFQTAALRMPAQIERVEIFTSEDPPKISYLFVEEASDSVPTSHVSVLSETGEVLAKFTAMRFSEIEGTPGVSGSMESLVHQIAWPPATPAEEPLLITKVILVSPDATARAQYAATLPTQVQSFQFSTTEDFFSNASSLPLEKGTVVAYIPGEVASLAEVPAASESFTWNLLELIKFIVNGSLPIKVFTLTSSVGDGQTPTALAQSPLIGLARIIASEHPDLGSLIDIEEPKIPLSTMRYIQGADVIRISDGIARVSRFRSLPRTKLRPASEGPRLLPRPDGTYLITGGLGILGLEVADFLVEKGARRLLLISRRALPPRRTWDQVSEDLQPTIAKIRLLESRGASVHVLPLDITKPDAVEQLSTALDRLSLPAVQGVVHAAGVLDNEMVLQTTRDAFNRVLAPKIAGALALHEVFPPKSVDFFVMFSSCGNLVGFTGQASYGSGNAFLDTLATHRARLGDSGAVAFQWTAWRGLGMGSSTDFINAELEAKGITDVTRDEAFAAWQHLAKYDIDHGVVLRSLAIDDGEPVPVPILNDIVVRRVSELSGSAQAAAGSSGNDAVPSSGPELKAYLDEKIRGCVAKVLQMTAEDVDSKAALADLGVDSVMTVTLRRQLQQTLKIPVPPTLTWSHPTVSHLVVWFAEKIGK