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


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.

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Fig. 1: Biosynthetic potential of the Ehrlich pathway.
Fig. 2: Theoretical and practical aspects of CO2 fixation by a decarboxylase.
Fig. 3: Enzymatic parameters for the decarboxylation of MTOB.
Fig. 4: Enzymatic parameters for determining the chemical carboxylation equilibrium.


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The authors thank Evonik Industries for financial support, and T. Haas and H. Jakob for fruitful discussions. They are also grateful to C. Schmid, C. Dawid and T. Hofmann at TUM for LC-MS/MS measurements.

Author information

A.S. developed the concept of the study. J.M. and L.E. contributed to planning the experiments, and performed the measurements. All authors conducted data analysis and discussed the results. J.M. and A.S. wrote the paper.

Correspondence to Arne Skerra.

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A.S. and L.E. declare inventorship on a patent application claiming subject matter of this study (WO 2018/104143 A1).

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Martin, J., Eisoldt, L. & Skerra, A. Fixation of gaseous CO2 by reversing a decarboxylase for the biocatalytic synthesis of the essential amino acid l-methionine. Nat Catal 1, 555–561 (2018).

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