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

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 similar to 1.3 mu mol/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.