Advances in the Applications of Metabolic Engineering in Synthetic Biology

Abstract

Metabolic engineering, a core pillar of synthetic biology, enables the precise reprogramming of cellular metabolism for efficient production of valuable compounds. This review outlines recent advances in genome editing, pathway construction, and dynamic regulation strategies that underpin modern metabolic engineering. Emerging tools such as CRISPR-derived editors, machine learning-guided design, and automated high-throughput workflows have accelerated the design–build–test–learn cycle and enabled predictive strain optimization. Applications span microbial cell factories, mammalian and plant hosts, cell-free biosynthesis systems, synthetic consortia, and non-traditional chassis such as photosynthetic microbes, extremophiles, and filamentous fungi. These engineered systems have facilitated the biosynthesis of fuels, pharmaceuticals, specialty chemicals, and nutraceuticals, often under environmentally sustainable conditions. Challenges remain in scaling processes, overcoming metabolic bottlenecks, and ensuring biosafety in complex systems. Nevertheless, the integration of systems biology, artificial intelligence, and synthetic design is ushering in a new era of intelligent and modular biomanufacturing. Continued innovation in chassis development, global metabolic rewiring, and closed-loop automation will further expand the capabilities and impact of metabolic engineering across biotechnology and industrial applications.