Guiding efficient microbial synthesis of non-natural chemicals by physicochemical properties of reactants

The recent progress in sustainable chemistry and in synthetic biology increased the interest of chemical and pharmaceutical industries to implement microbial processes for chemical synthesis. However, most organisms used in biotechnological applications are not evolved by Nature for the production of hydrophobic, non-charged, volatile, or toxic compounds. In order to overcome this discrepancy, bioprocess design should consist of an integrated approach addressing pathway, cellular, reaction, and process engineering. Highlighting selected examples, we show that surprisingly often Nature provides conceptual solutions to enable chemical synthesis. Complemented by established methods from (bio)chemical and metabolic engineering, these concepts offer potential strategies yet to be explored and translated into innovative technical solutions enabling sustainable microbial production of non-natural chemicals.