Biotechnological Advances in L-DOPA Biosynthesis and Production

IF 3.6 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Biotechnology and Bioengineering Pub Date : 2025-06-23 DOI:10.1002/bit.70011

Hongmei Han, Yue Chen, Lingtian Wu, Yongsheng Wang, Yibo Zhu

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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.

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左旋多巴生物合成与生产的生物技术进展。

在过去的60年里，左旋多巴（3,4-二羟基苯基-l-丙氨酸）一直是治疗帕金森病（PD）的主要药物，帕金森病是一种与多巴胺耗竭有关的退行性大脑疾病。因此，利用微生物代谢工程或酶促过程的生物技术方法已被广泛探索作为生产左旋多巴的有前途的替代品。这些方法不仅提高了转化效率和对映体选择性，而且具有成本效益和环境可持续性。代谢工程策略已被用于改造大肠杆菌菌株，使其能够通过调节碳代谢途径从葡萄糖中积累左旋多巴。此外，表达酪氨酸酶、对羟基苯乙酸3-羟化酶（PHAH）或酪氨酸苯酚裂解酶（TPL）的微生物系统已被用于左旋多巴的生物合成。本文综述了目前左旋多巴生物合成和生物技术生产策略的研究进展，并对其优缺点进行了比较分析。此外，我们讨论了生物技术驱动的左旋多巴生产的前景，强调了其工业应用和大规模生产的可行性。

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来源期刊

Biotechnology and Bioengineering 工程技术-生物工程与应用微生物

CiteScore

7.90

自引率

5.30%

发文量

280

审稿时长

2.1 months

期刊介绍： Biotechnology & Bioengineering publishes Perspectives, Articles, Reviews, Mini-Reviews, and Communications to the Editor that embrace all aspects of biotechnology. These include: -Enzyme systems and their applications, including enzyme reactors, purification, and applied aspects of protein engineering -Animal-cell biotechnology, including media development -Applied aspects of cellular physiology, metabolism, and energetics -Biocatalysis and applied enzymology, including enzyme reactors, protein engineering, and nanobiotechnology -Biothermodynamics -Biofuels, including biomass and renewable resource engineering -Biomaterials, including delivery systems and materials for tissue engineering -Bioprocess engineering, including kinetics and modeling of biological systems, transport phenomena in bioreactors, bioreactor design, monitoring, and control -Biosensors and instrumentation -Computational and systems biology, including bioinformatics and genomic/proteomic studies -Environmental biotechnology, including biofilms, algal systems, and bioremediation -Metabolic and cellular engineering -Plant-cell biotechnology -Spectroscopic and other analytical techniques for biotechnological applications -Synthetic biology -Tissue engineering, stem-cell bioengineering, regenerative medicine, gene therapy and delivery systems The editors will consider papers for publication based on novelty, their immediate or future impact on biotechnological processes, and their contribution to the advancement of biochemical engineering science. Submission of papers dealing with routine aspects of bioprocessing, description of established equipment, and routine applications of established methodologies (e.g., control strategies, modeling, experimental methods) is discouraged. Theoretical papers will be judged based on the novelty of the approach and their potential impact, or on their novel capability to predict and elucidate experimental observations.