Biotechnological Advances in L-DOPA Biosynthesis and Production

l-DOPA (3,4-dihydroxyphenyl-l-alanine) has been the primary medication for treating Parkinson's disease (PD), a degenerative brain disorder related to dopamine depletion, for the past six decades. As a result, biotechnological approaches utilizing metabolic engineering in microorganisms or enzymatic processes have been extensively explored as promising alternatives for l-DOPA production. These methods not only enhance conversion efficiency and enantioselectivity but are also cost-effective and environmentally sustainable. Metabolic engineering strategies have been employed to engineer Escherichia coli strains capable of accumulating l-DOPA from glucose by regulating carbon metabolism pathways. Additionally, microbial systems expressing tyrosinase, p-hydroxyphenylacetate 3-hydroxylase (PHAH), or tyrosine phenol-lyase (TPL) have been utilized for l-DOPA biosynthesis. In this review, we summarize current advancements in l-DOPA biosynthesis and biotechnological production strategies, providing a comparative analysis of their advantages and limitations. Moreover, we discuss the promise of biotech-driven l-DOPA production, emphasizing its industrial applications and large-scale production feasibility.