biostudies-literatureLohr NADeutsche Forschungsgemeinschafte202200649https://www.ebi.ac.uk/biostudies/studies/S-EPMC10108026biostudies-literatureUnknown24(3)The nonreducing iterative type I polyketide synthases (NR-PKSs) CoPKS1 and CoPKS4 of the webcap mushroom Cortinarius odorifer share 88 % identical amino acids. CoPKS1 almost exclusively produces a tricyclic octaketide product, atrochrysone carboxylic acid, whereas CoPKS4 shows simultaneous hepta- and octaketide synthase activity and also produces the bicyclic heptaketide 6-hydroxymusizin. To identify the region(s) controlling chain length, four chimeric enzyme variants were constructed and assayed for activity in Aspergillus niger as heterologous expression platform. We provide evidence that the β-ketoacyl synthase (KS) domain determines chain length in these mushroom NR-PKSs, even though their KS domains differ in only ten amino acids. A unique proline-rich linker connecting the acyl carrier protein with the thioesterase domain varies most between these two enzymes but is not involved in chain length control.Chembiochem : a European journal of chemical biologyThe Ketosynthase Domain Controls Chain Length in Mushroom Oligocyclic Polyketide Synthases.PMC10108026HO2515/8-1Eisen FMuller MGressler MHoffmeister DLohr NAHuttel WUrban MCPlatz LfalseThe Ketosynthase Domain Controls Chain Length in Mushroom Oligocyclic Polyketide Synthases.The nonreducing iterative type I polyketide synthases (NR-PKSs) CoPKS1 and CoPKS4 of the webcap mushroom Cortinarius odorifer share 88 % identical amino acids. CoPKS1 almost exclusively produces a tricyclic octaketide product, atrochrysone carboxylic acid, whereas CoPKS4 shows simultaneous hepta- and octaketide synthase activity and also produces the bicyclic heptaketide 6-hydroxymusizin. To identify the region(s) controlling chain length, four chimeric enzyme variants were constructed and assayed for activity in Aspergillus niger as heterologous expression platform. We provide evidence that the β-ketoacyl synthase (KS) domain determines chain length in these mushroom NR-PKSs, even though their KS domains differ in only ten amino acids. A unique proline-rich linker connecting the acyl carrier protein with the thioesterase domain varies most between these two enzymes but is not involved in chain length control.2023-01-01T00:00:00Z2023 Feb2025-07-10T03:08:15.415Z2025-04-06T11:22:11.583ZS-EPMC101080263650760010.1002/cbic.202200649