The cofactor challenge in synthetic methylotrophy: bioengineering and industrial applications.

Jan L Krüsemann, Vittorio Rainaldi, Charles Ar Cotton, Nico J Claassens, Steffen N Lindner

Current opinion in biotechnology 2023 Aug

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Methanol is a promising feedstock for industrial bioproduction: it can be produced renewably and has high solubility and limited microbial toxicity. One of the key challenges for its bio-industrial application is the first enzymatic oxidation step to formaldehyde. This reaction is catalysed by methanol dehydrogenases (MDH) that can use NAD+, O2 or pyrroloquinoline quinone (PQQ) as an electron acceptor. While NAD-dependent MDH are simple to express and have the highest energetic efficiency, they exhibit mediocre kinetics and poor thermodynamics at ambient temperatures. O2-dependent methanol oxidases require high oxygen concentrations, do not conserve energy and thus produce excessive heat as well as toxic H2O2. PQQ-dependent MDH provide a good compromise between energy efficiency and good kinetics that support fast growth rates without any drawbacks for process engineering. Therefore, we argue that this enzyme class represents a promising solution for industry and outline engineering strategies for the implementation of these complex systems in heterologous hosts. Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Citation

Jan L Krüsemann, Vittorio Rainaldi, Charles Ar Cotton, Nico J Claassens, Steffen N Lindner. The cofactor challenge in synthetic methylotrophy: bioengineering and industrial applications. Current opinion in biotechnology. 2023 Aug;82:102953