Fixation of gaseous CO2 by reversing a decarboxylase for the biocatalytic synthesis of the essential amino acid l-methionine

Abstract

The use of CO2 as a building block for the synthesis of bulk chemicals appears highly attractive but has not been realized in industrial biotechnology due to the complexity and costly energy balance of conventional anabolic biosynthesis. Here, we describe the biocatalytic preparation of l-methionine from the abundant industrial intermediate methional under direct incorporation of CO2 by reversing the catabolic Ehrlich pathway. Despite unfavourable chemical equilibrium (1/554 M−1), the decarboxylase KdcA revealed half-maximal activity for its reverse reaction at astonishingly low CO2 pressure (320 kPa). Accordingly, it was possible to synthesize l-methionine under a 2 bar CO2 atmosphere when coupled to an energetically favourable transaminase or amino acid dehydrogenase reaction. Similarly, l-leucine and l-isoleucine were prepared via biocatalytic carboxylation of 3- or 2-methylbutanal, respectively. Our findings open a biotechnological route towards industrial products and enable further syntheses involving the fixation of gaseous CO2 by simply applying decarboxylases in the reverse mode. The preparation of functionalized amino acids from inexpensive aldehydes is challenging. This work describes the biocatalytic synthesis of l-methionine by applying gaseous CO2 pressure and a coupled amination step to drive the unfavoured equilibrium of a reverse carboxylation reaction.