Riboflavin is an essential nutrient for humans and animals, and its derivatives flavin mononucleotide (FMN) and flavin adenine dinucleotide (FAD) are cofactors in the cells. Therefore, riboflavin and its derivatives are widely used in the food, pharmaceutical, nutraceutical and cosmetic industries. Advances in biotechnology have led to a complete shift in the commercial production of riboflavin from chemical synthesis to microbial fermentation. In this review, we provide a comprehensive review of biotechnologies that enhance riboflavin production in microorganisms, as well as representative examples. Firstly, the synthesis pathways and metabolic regulatory processes of riboflavin in microorganisms; and the current strategies and methods of metabolic engineering for riboflavin production are systematically summarized and compared. Secondly, the using of systematic metabolic engineering strategies to enhance riboflavin production is discussed, including laboratory evolution, histological analysis and high-throughput screening. Finally, the challenges for efficient microbial production of riboflavin and the strategies to overcome these challenges are prospected.

核黄素是人和动物必需的营养素，其衍生物黄素单核苷酸（FMN）和黄素腺嘌呤二核苷酸（FAD）是细胞内的辅助因子。因此，核黄素及其衍生物广泛用于食品、制药、保健品和化妆品行业。生物技术的进步导致核黄素的商业生产从化学合成完全转变为微生物发酵。在这篇综述中，我们对提高微生物中核黄素产量的生物技术以及具有代表性的例子进行了全面的综述。一、核黄素在微生物中的合成途径和代谢调控过程；并对目前核黄素生产代谢工程的策略和方法进行了系统的总结和比较。第二，讨论了使用系统代谢工程策略来提高核黄素产量，包括实验室进化、组织学分析和高通量筛选。最后，展望了高效微生物生产核黄素的挑战以及克服这些挑战的策略。