Strategies and challenges with the microbial conversion of methanol to high‐value chemicals

Abstract

As alternatives to traditional fermentation substrates, methanol (CH3OH), carbon dioxide (CO2) and methane (CH4) represent promising one‐carbon (C1) sources that are readily available at low‐cost and share similar metabolic pathway. Of these C1 compounds, methanol is used as a carbon and energy source by native methylotrophs, and can be obtained from CO2 and CH4 by chemical catalysis. Therefore, constructing and rewiring methanol utilization pathways may enable the use of one‐carbon sources for microbial fermentations. Recent bioengineering efforts have shown that both native and nonnative methylotrophic organisms can be engineered to convert methanol, together with other carbon sources, into biofuels and other commodity chemicals. However, many challenges remain and must be overcome before industrial‐scale bioprocessing can be established using these engineered cell refineries. Here, we provide a comprehensive summary and comparison of methanol metabolic pathways from different methylotrophs, followed by a review of recent progress in engineering methanol metabolic pathways in vitro and in vivo to produce chemicals. We discuss the major challenges associated with establishing efficient methanol metabolic pathways in microbial cells, and propose improved designs for future engineering.

Closing the Loop: Autonomous High-Throughput Strain Characterisation from Frozen Cell Bank to Product Assay

“…The first one includes usage of methanol as a solvent, which could impede the adhesion of MTP parts, especially the transparent bottom plate. As a potential benefit, methanol is toxic to C. glutamicum and many other microbial systems [21], acting as a second disinfectant. For the second strategy with medium, the ability to restore sterile and consistent process conditions needed to be validated.…”

Integrating greenhouse gas capture and C1 biotechnology: a key challenge for circular economy

“…However, CH 3 OH can inhibit the growth of microorganisms under aerobic conditions, mainly because of the high reactivity of its toxic downstream metabolite H 2 CO. Methylotrophs, including bacteria, such as Bacillus methanolicus, and yeasts, such as Pichia pastoris, can use CH 3 OH as a carbon and energy source. With some exceptions such as P. pastoris , the use of native methylotrophic microorganisms suffers from the drawbacks of poor genetic availability and low metabolic yield, and therefore, engineering non‐native methylotrophic microbes has been used to convert methanol into value‐added products (Zhang et al ., 2019; Zhan et al ., 2021). Different bioengineering efforts have shown that these recombinant organisms can be engineered to convert CH 3 OH into biofuels and other commodity chemicals (Bennett et al ., 2018; Chistoserdova, 2018; Antoniewicz, 2019; Zhu et al ., 2020).…”

In vivo implementation of a synthetic metabolic pathway for the carbon-conserving conversion of glycolaldehyde to acetyl-CoA

“…The use of atmospheric or industry-released CO 2 as feedstock for production of value-added chemicals is an attractive means to reduce greenhouse gas emissions in a circular economy ( Whipple and Kenis, 2010 ). (Electro)chemical conversion of CO 2 to methanol or syngas ( Goeppert et al, 2014 ) followed by microbial fermentation is a promising strategy for the biochemical valorization of CO 2 ( Cotton et al, 2020 ; Gavala et al, 2021 ; Zhan et al, 2021 ). However, the technical implementation of microbial production processes using one-carbon (C 1 ) substrates remains challenging which is mainly due to the thermodynamically restricted product panel of strictly anaerobic syngas fermentations ( Takors et al, 2018 ; Teixeira et al, 2018 ), and the extremely high oxygen demand of methanol-based bioprocesses ( Frazão and Walther, 2020 ).…”