Cross-linking of a polyketide synthase domain leads to a recyclable biocatalyst for chiral oxygen heterocycle synthesis

The potential of polyketide synthase (PKS) domains for chemoenzymatic synthesis can often not be tapped due to their low stability and activity in vitro . In this proof-of-principle study, the immobilisation of the heterocycle-forming PKS domain AmbDH3 as a cross-linked enzyme aggregate (CLEA) is described. The AmbDH3-CLEA showed good activity recovery, stability and recyclability. Repetitive reactions on the semi-preparative scale were performed with high conversion and isolated yield. Similar to that observed for the free enzyme, the aggregate retained substrate tolerance and the ability for kinetic resolution. This first example of a successful enzymatic PKS domain immobilisation demonstrates that cross-linking can in principle be applied to this type of enzyme to increase its applicability for chemoenzymatic synthesis. Cross-linking of the polyketide synthase domain AmbDH3 led to an active aggregate with improved properties for the chemoenzymatic synthesis of chiral oxygen heterocycles, such as recyclability and facile purification.