The Ketosynthase Domain Controls Chain Length in Mushroom Oligocyclic Polyketide Synthases

Overview

Journal Chembiochem

Specialty Biochemistry

Date 2022 Dec 12

PMID 36507600

Authors

Nikolai A Lohr

Maximilian C Urban

Frederic Eisen

Lukas Platz

Wolfgang Huttel

Markus Gressler

Michael Muller

Dirk Hoffmeister

Affiliations

Soon will be listed here.

Abstract

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.

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