A Self‐Regulated Process from Bench to Pilot Production of Non‐Natural Heterocycles Using Halohydrin Dehalogenases

Abstract Halohydrin dehalogenases (HHDHs) have demonstrated significant potential as biocatalysts for synthesizing industrial heterocyclic compounds and chiral alkanolamines from aromatic substrates with NaOCN that are not feasible through chemosynthesis. To further study the HHDH reaction in real industrial applications, a diverse panel of HHDHs has been screened for their ability to convert aliphatic cyclohexene oxide. By using the best HHDH variant in form of a whole cell biocatalyst, a novel chemical process, regulated by the cascaded chemoenzymatic reactions for pilot‐scale ring‐opening reactions, has been successfully developed. Using the best HHDH hit in whole‐cell form provides a viable bio‐catalytic approach for the synthesis of related fine chemicals. Our research provides a promising strategy for scaling up non‐native ring‐opening reactions from the laboratory to industrial applications.