Abstract
Industrial application of the natural deazaflavin cofactor F(420) has high potential for the enzymatic synthesis of high value compounds. It can offer an additional range of chemistry to the use of well-explored redox cofactors such as FAD and their respective enzymes. Its limited access through organisms that are rather difficult to grow has urged research on the heterologous production of F(420) using more industrially relevant microorganisms such as Escherichia coli. In this study, we demonstrate the possibility of producing this cofactor in a robust and widely used industrial organism, Saccharomyces cerevisiae, by the heterologous expression of the F(420) pathway. Through careful selection of involved enzymes and some optimization, we achieved an F(420) yield of ∼1.3 μmol/L, which is comparable to the yield of natural F(420) producers. Furthermore, we showed the potential use of F(420)-producing S. cerevisiae for F(420)-dependent bioconversions by carrying out the whole-cell conversion of tetracycline. As the first demonstration of F(420) synthesis and use for bioconversion in a eukaryotic organism, this study contributes to the development of versatile bioconversion platforms.