Metabolic engineering strategies for constructing methylotrophic cell factories

Pei Zhou , Yang Sun , Yinbiao Xu , Yupeng Liu , Hua Li

Systems Microbiology and Biomanufacturing ›› 2025, Vol. 5 ›› Issue (4) : 1371 -1381.

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Systems Microbiology and Biomanufacturing ›› 2025, Vol. 5 ›› Issue (4) :1371 -1381. DOI: 10.1007/s43393-025-00385-w
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Metabolic engineering strategies for constructing methylotrophic cell factories
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Abstract

Methanol is a one-carbon compound that has emerged as a promising carbon source for microbial bioproduction due to its abundance and sustainability. Despite the development of synthetic methylotrophic cell factories, challenges, such as the accumulation of toxic intermediates and suboptimal growth rates, have hindered their industrial application. This review summarizes the engineering strategies for methylotrophic cell factory synthesis, including pathway engineering for methanol assimilation optimization, detoxification methods targeting formaldehyde accumulation, and optimization of cell resource utilization. Future challenges and prospects of advancing microbial methanol assimilation in biotechnological applications are also highlighted.

Keywords

Methanol assimilation / Metabolic engineering / Pathway engineering / Adaptive laboratory evolution

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Pei Zhou, Yang Sun, Yinbiao Xu, Yupeng Liu, Hua Li. Metabolic engineering strategies for constructing methylotrophic cell factories. Systems Microbiology and Biomanufacturing, 2025, 5(4): 1371-1381 DOI:10.1007/s43393-025-00385-w

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Funding

Key Research and Development Project of Henan Province(231111310700)

Key Technologies R&D Program of Henan Province (252102311184)

Key Research Projects of Higher Education Institutions in Henan Province(25A416005)

Natural Science Foundation of Henan Province(252300420649)

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Jiangnan University

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