Whole-cell based synthetic enzyme cascades-light and shadow of a promising technology.

Mimicking Nature by biocatalytic cascade reactions in a whole-cell environment is a revolutionary development in multistep synthesis for the production of bulk and fine chemicals. In the past decade, several proof of concept success stories demonstrated the power of those synthetic cascades and paved the road for future industrial applications. Although enzymes and their promiscuity are best suited to construct such artificial pathways, the complexity and the lack of understanding of the cellular machinery slowed down this progress significantly. In this review, recent achievements in the field of whole-cell biocatalysis are described, challenges and hidden traps that have to be overcome are depicted, and strategies are illustrated how to increase overall cascade productivity.