Integrating synthetic biology and process engineering for enhanced isobutanol biosynthesis yield and sustainability

Isobutanol holds significant potential as a next-generation biofuel and platform chemical, offering a viable alternative to petroleum across various industries, including pharmaceuticals, and fine chemicals. Biosynthesis has emerged as a highly advantageous approach for isobutanol production, surpassing conventional chemical synthesis methods in terms of environmental sustainability, safety, and ecological compatibility. Consequently, the field of isobutanol biosynthesis has garnered increasing interest. This review provides an overview of recent breakthroughs in isobutanol biosynthesis and explores strategies aimed at improving its production yield from both biological and engineering perspectives. On the biological front, the exploration and optimization of enzymatic pathways, metabolic engineering techniques to enhance precursor availability and flux, and cellular engineering approaches to improve strain tolerance and production efficiency are meticulously analysed. Additionally, engineering aspects such as in situ product removal methods and biomass fermentation are introduced, as they significantly contribute to enhancing yields and economy. Despite the immense promise of isobutanol biosynthesis, several challenges require attention. The modification of enzymatic and metabolic pathways is crucial for increasing production efficiency and yield. The adoption of high-throughput screening techniques becomes indispensable for identifying and selecting optimal strains and enzymes with improved characteristics. Furthermore, the cytotoxic nature and volatility of isobutanol pose additional hurdles, leading to losses during the production process. By effectively addressing these challenges and advancing our understanding of isobutanol biosynthesis, we can pave the way for more efficient and sustainable production methods. This review aims to provide valuable insights and inspiration to researchers in the field, with the ultimate objective of accelerating the development and application of isobutanol biosynthesis.