Engineering microbial cell factories for the production of lycopene: Advances and perspectives

Lycopene, a high-value carotenoid widely used as a natural colorant and antioxidant in the agri-food industry, is currently produced in microbial cell factories. We first summarize recent advances in microbial cell factory-based lycopene production. Next, we review metabolic engineering strategies that enhance lycopene biosynthesis-pathway flux modulation, cofactor optimization, transcription factor engineering, efflux engineering, etc. We also spotlight the application of emerging technologies-multi-enzyme scaffolding, high-throughput screening and machine learning-in lycopene synthesis. Aligning with green-manufacturing goals, we review progress on lycopene biosynthesis from feedstocks such as lignocellulose, methanol, CO₂ and PET. Finally, we discuss strategies for enhancing cellular robustness to mitigate scale-up constraints. The integrated approaches presented here provide insights for overproducing lycopene, other carotenoids and structurally related terpenoids.