# Advances in synthetic biology for engineering methylotrophic microbial cell factories

## TL;DR

This paper reviews recent synthetic biology advances to improve microbes that can use methanol, aiming to support sustainable industrial production.

## Contribution

The paper provides a comprehensive review of strategies to engineer methylotrophic microbes for efficient methanol utilization.

## Key findings

- Efficient methanol assimilation pathways have been developed using synthetic biology techniques.
- Methanol dehydrogenase has been engineered to improve oxidation efficiency in methylotrophs.
- Strategies like redox balance optimization and adaptive evolution enhance microbial robustness.

## Abstract

Methanol, a renewable non-food C1 substrate, holds great promise as a feedstock for sustainable biomanufacturing and carbon neutral production. However, its industrial application is hindered by low methanol assimilation efficiency in most microbes. Recent advances in synthetic biology and metabolic engineering have enabled the development of methylotrophic microbial cell factories through strategies including building efficient methanol-utilizing pathways, engineering methanol dehydrogenase for enhanced oxidation efficiency, and optimizing redox balance via cofactor utilization. Additionally, approaches such as mitigating the accumulation of toxic metabolites and adaptive laboratory evolution have been adopted to improve the robustness of synthetic methylotrophs. This review summarizes these innovations and provides a blueprint for rationally designing high-performance microbial platforms to facilitate industrial methanol utilization and advance sustainable development.