Biotechnological Advances in L‐DOPA Biosynthesis and Production

ABSTRACT 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.