Synthetic biology approaches to improve tolerance of inhibitors in lignocellulosic hydrolysates

Increasing attention is being focused on using lignocellulose for valuable products. Microbial decomposition can convert lignocellulose into renewable biofuels and other high-value bioproducts, contributing to sustainable development. However, the presence of inhibitors in lignocellulosic hydrolysates can negatively affect microorganisms during fermentation. Improving microbial tolerance to these hydrolysates is a major focus in metabolic engineering. Traditional detoxification methods increase costs, so there is a need for cheap and efficient cell-based detoxification strategies. Synthetic biology approaches offer several strategies for improving microbial tolerance, including redox balancing, membrane engineering, omics-guided technologies, expression of protectants and transcription factors, irrational engineering, cell flocculation, and other novel technologies. Advances in molecular biology, high-throughput sequencing, and artificial intelligence (AI) allow for precise strain modification and efficient industrial production. Developing AI-based computational models to guide synthetic biology efforts and creating large-scale heterologous libraries with automation and high-throughput technologies will be important for future research. •The compositions of lignocellulose, treatment methods and its derivatives are described.•Mechanisms of microbial damage by inhibitors in lignocellulosic hydrolysates are delineated.•Efforts on enhancing stress-resistance through synthetic biology approaches were summarized and discussed.•AI-based computational models can guide future researches.