Metabolic Engineering of Thermophilic Bacteria for Biotechnological Applications

Metabolic engineering of thermophilic bacteria harnesses the natural advantages of heat‐tolerant microbes to produce chemicals, fuels and enzymes under industrially favourable conditions. Elevated reaction temperatures accelerate biochemical rates, improve substrate solubility and minimise contamination risks, while reducing cooling demands in large‐scale fermentations. Thermophilic hosts such as Geobacillus, Parageobacillus and Thermus species combine intrinsic thermostable enzyme systems with expanding genetic toolkits to enable pathway rewiring, genome editing and dynamic control of gene expression. Key objectives include the consolidation of saccharification and fermentation steps into a single process, enhancement of lignocellulose degradation via specialised carbohydrate‐active loci, and redirection of carbon flux towards high‐value targets such as bioethanol, organic acids and fine chemicals. Recent advances in inducible regulation, CRISPR‐based editing and high‐throughput screening have accelerated chassis development, yet challenges remain in balancing pathway thermodynamics, minimising off‐target mutations and achieving robust performance at elevated temperatures. By integrating systems biology, protein engineering and process optimisation, the field is poised to deliver sustainable, cost‐effective biomanufacturing platforms that exploit the unique physiology of thermophiles on a global scale.

Research from Nature Portfolio

Recent studies have demonstrated the pivotal role of the phosphoenolpyruvate:carbohydrate phosphotransferase system in the thermophilic bacterium Parageobacillus thermoglucosidasius. Systematic deletion of the common enzyme I revealed a suite of carbohydrates—including cellobiose, fructose and trehalose—whose uptake and phosphorylation are strictly PTS‐dependent. Further characterisation of individual transport modules identified six distinct PTS variants essential for translocation of specific sugars, laying a molecular foundation for targeted engineering of sugar utilisation pathways. This work provides a detailed map of carbohydrate flux control in a thermophilic chassis and offers direct routes to optimise whole‐cell biocatalysis for diverse feedstocks.

Metabolic Engineering of Thermophilic Bacteria for Biotechnological Applications publication trend

The graph below shows the total number of articles in metabolic engineering of thermophilic bacteria for biotechnological applications across all publications each year (not limited to Nature Index journals).

Technical terms

Thermophilic bacteria: Microorganisms that grow optimally at temperatures above 50 °C, often possessing heat‐stable enzymes and membranes.

Consolidated Bioprocessing (CBP): An integrated strategy combining enzyme production, substrate hydrolysis and fermentation in a single organism or reactor.

Phosphotransferase system (PTS): A bacterial transport mechanism that couples carbohydrate uptake with phosphorylation, using phosphoenolpyruvate as a phosphoryl donor.

Riboswitch: A regulatory RNA element that alters gene expression in response to binding of a small molecule ligand.

Microbial chassis: A host organism engineered as a platform for heterologous pathway expression and metabolic control.

References

1. Parageobacillus thermoglucosidasius as an emerging thermophilic cell factory. Metabolic Engineering (2024).
2. Parageobacillus thermoglucosidasius Strain Engineering Using a Theophylline Responsive RiboCas for Controlled Gene Expression. ACS Synthetic Biology (2024).
3. Functional characterization of the phosphotransferase system in Parageobacillus thermoglucosidasius. Scientific Reports (2023).