Current advances in the bioactivity, biosynthesis, and production enhancement strategies of 5-methyltetrahydrofolate from Moringa oleracea Lam.: a comprehensive review

• Systematic Summary of Folate Classification and Bioactivities: This review comprehensively elucidates the molecular structures, physiological functions, and critical roles of folate in human health, with particular emphasis on its contributions to birth defect prevention, neurological system maintenance, and anemia treatment.

• Focus on the Core Advantages of the Natural Active Form 5-MTHF: We highlight 5-methyltetrahydrofolate (5-MTHF) as the only folate derivative capable of directly participating in the methylation cycle, thereby overcoming the metabolic limitations of synthetic folate and addressing the supplementation needs of special populations (e.g., individuals with folate metabolism disorders).

• Proposal of Synthetic Biology-Driven Strategies for 5-MTHF Production: To address the challenges of low extraction yield and poor stability of natural 5-MTHF, this review evaluates innovative synthetic biology approaches for constructing efficient cell factories and achieving green, sustainable production, providing both theoretical and technical support for large-scale preparation.

• Interdisciplinary Application Perspectives: By bridging fundamental research with industrial demands, we propose transformative applications of 5-MTHF in precision nutrition (e.g., specialized diets for pregnant women and the elderly), disease prevention (e.g., cardiovascular and neurodegenerative diseases), and pharmaceutical development, offering cross-disciplinary research insights for food science, nutrition, and biomedical fields.

• Special Focus on Health Solutions for Specific Populations: We emphasize the irreplaceable value of 5-MTHF for populations with folate metabolism disorders, promoting the development of personalized nutritional intervention strategies to address clinical gaps in current folate supplementation approaches.