Equipping Saccharomyces cerevisiae with an Additional Redox Cofactor Allows F420-Dependent Bioconversions in Yeast

Abstract

Industrial application of the natural deazaflavin cofactor F420 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 F420 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 F420 pathway. Through careful selection of involved enzymes and some optimization, we achieved an F420 yield of ∼1.3 μmol/L, which is comparable to the yield of natural F420 producers. Furthermore, we showed the potential use of F420-producing S. cerevisiae for F420-dependent bioconversions by carrying out the whole-cell conversion of tetracycline. As the first demonstration of F420 synthesis and use for bioconversion in a eukaryotic organism, this study contributes to the development of versatile bioconversion platforms.