Synthetic methylotrophy: Engineering microbes for sustainable biomanufacturing from C1 compounds

Vaibhav Vinod Phokmare , Satish Chandra Pandey , Prashant Khare

Systems Microbiology and Biomanufacturing ›› 2025, Vol. 5 ›› Issue (3) : 1000 -1015.

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Systems Microbiology and Biomanufacturing ›› 2025, Vol. 5 ›› Issue (3) : 1000 -1015. DOI: 10.1007/s43393-025-00379-8
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Synthetic methylotrophy: Engineering microbes for sustainable biomanufacturing from C1 compounds

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Abstract

Recycling greenhouse gases from industrial emissions is necessary for a genuine circular carbon economy. One-carbon (C1) compounds like methanol produced from greenhouse gases and its subsequent use as a feedstock hold great promise in driving the next generation of biomanufacturing. This review explores the emerging field of synthetic methylotrophy, which focuses on engineering microbial cell factories to convert methanol into useful bioproducts like industrial chemicals, pharmaceuticals, fuels, and food. Native methylotrophs have natural pathways for methanol utilization, but obstacles such as metabolic inefficiency and the availability of genetic modification tools limit their use. In contrast, Synthetic methylotrophy makes use of model organisms such as Escherichia coli and Saccharomyces cerevisiae, which can be genetically altered to enhance the efficiency of bioconversion and methanol utilization. Although formaldehyde detoxification and enzyme optimization have improved recently due to developments in metabolic engineering, there are still many obstacles to overcome, such as limited methanol uptake and toxicity problems. The recent developments in synthetic methylotrophy are highlighted in this review, which also stresses the necessity of integrating advanced synthetic biology techniques and performing further research into metabolic pathways of methanol assimilation. Together with a consideration of the techno-economic aspects affecting the scalability of these novel processes, the potential for C1-based biomanufacturing to support sustainable production methods is emphasized.

Keywords

Biomanufacturing / One-carbon (C1) compound / Methanol / Synthetic methylotrophy / Metabolic engineering

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Vaibhav Vinod Phokmare, Satish Chandra Pandey, Prashant Khare. Synthetic methylotrophy: Engineering microbes for sustainable biomanufacturing from C1 compounds. Systems Microbiology and Biomanufacturing, 2025, 5(3): 1000-1015 DOI:10.1007/s43393-025-00379-8

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