Concatenating microorganisms, chemical catalysts, and enzymes for the synthesis of ethyl formate from renewables

Abstract

Alternative chemical synthesis routes and the (re)utilization of CO₂ are crucial for the development of a circular bioeconomy. To establish sustainable production methods, concatenating various catalysts allows for leveraging the unique advantages of each catalyst type. During process development, however, the reaction conditions must be harmonized, the catalyst compatibility must be examined, bottlenecks must be identified, and thus the operating window for the best process mode must be found. Here, we present ethyl formate synthesis from glucose, which is achieved by concatenating three catalysts: the yeast Saccharomyces cerevisiae, a ruthenium catalyst, and a lipase in an immobilized enzyme formulation. This study identifies the parameters that require investigation when combining different catalyst types and integrating CO₂ as an alternative raw material. Parameters such as product stability across different reaction systems, product distribution in a two-phase system using different organic solvents, and catalyst compatibility were studied. Candida antarctica lipase B was identified as a suitable biocatalyst for the enzymatic esterification of formic acid and ethanol. The catalyst compatibility is shown. However, the aqueous phase, necessary for yeasts, conflicts with product stability and catalyst activity. The desired one-pot, one-step process could not be realized. As a consequence, the process can only be efficiently performed in two steps, because in a one-pot, one-step reaction, the product yield was low. The concept of a concatenated ruthenium-catalyzed hydrogenation and lipase reaction can also be adapted to other formate esters starting from CO₂.