Safety Evaluation of N- trans -caffeoyltyramine Derived From a Strain of Yarrowia lipolytica Through Precision Fermentation

Abstract

N-trans-caffeoyltyramine (NCT) is a phenolic hydroxycinnamic acid amide naturally present in many plant crop species and is associated with immune response and many development processes. Little research has been done on the potential safety of NCT for use as an ingredient in conventional foods and beverages. This study assessed the safety of NCT derived from caffeic acid and produced using a genetically engineered strain Yarrowia lipolytica strain 3599_7 via precision fermentation through in vitro genotoxicity assays and a 90-day dietary oral toxicity study in rats. The Ames test was performed in bacterial strains and the highest dose tested was 5000.0 μg/plate in the presence and absence of S9. The in vitro mammalian micronucleus test was conducted in human peripheral blood lymphocytes in culture exposed to NCT at predetermined concentrations in the absence (4-hour and 24-hour exposure) and presence (4-hour exposure) of S9. NCT was not genotoxic as evident from the Ames and the in vitro micronucleus assay. NCT exhibited no adverse effects in the 90-day oral toxicity study up to the highest dose tested, where the no-observed-adverse-effect level was 1427 and 1983 mg/kg body weight/day in males and females, respectively.