State Key Laboratory of Microbial Metabolism, Joint International Research Laboratory of Metabolic and Developmental Sciences, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, China.
Microb Biotechnol. 2022 May;15(5):1610-1621. doi: 10.1111/1751-7915.14001. Epub 2022 Jan 10.
3, 4-Dihydroxyphenyl-l-alanine (l-DOPA) is a compound of high medical value and is considered effective as a treatment for Parkinson's disease. Currently, bioproduction of l-DOPA is mainly carried out by whole-cell catalysis mediated by recombinant Escherichia coli carrying heterogeneous tyrosine phenol lyase. Vibrio natriegens is increasingly attracting attention owing to its superiority, including extremely rapid growth and high soluble protein expression capacity. In this study, we attempt to develop an efficient whole-cell catalyst for l-DOPA production using V. natriegens as the chassis. The maximum soluble protein expression by V. natriegens was accomplished in 4 h at 37°C, which was equivalent to that achieved by E. coli in 16 h at 16°C. Furthermore, the maximum productivity reached over 10.0 g l h in the early stage of biocatalysis, nearly two-fold higher than previously reported. Approximately 54.0 g l l-DOPA was obtained with a catechol conversion rate greater than 95%. In conclusion, V. natriegens displays advantages, including rapid protein expression and catalytic rate in the catalysis process for l-DOPA production. These findings strongly suggest that V. natriegens has remarkable potential as a whole-cell catalysis chassis for the production of valuable chemicals.
3,4-二羟基苯丙氨酸（L-DOPA）是一种具有高医学价值的化合物，被认为是治疗帕金森病的有效药物。目前，L-DOPA 的生物生产主要通过携带异源酪氨酸酚裂解酶的重组大肠杆菌进行全细胞催化来实现。由于其生长速度极快、可溶性蛋白表达能力高，海栖热袍菌越来越受到关注。在本研究中，我们试图使用海栖热袍菌作为底盘来开发一种高效的 L-DOPA 生产全细胞催化剂。海栖热袍菌在 37°C 下 4 小时即可实现最大可溶性蛋白表达，相当于大肠杆菌在 16°C 下 16 小时的表达量。此外，生物催化的早期阶段的最大生产率超过 10.0 g·l-1·h-1，比之前报道的提高了近两倍。用邻苯二酚转化率大于 95%获得了约 54.0 g·l L-DOPA。总之，海栖热袍菌在 L-DOPA 生产的催化过程中表现出快速的蛋白表达和催化速率的优势。这些发现强烈表明，海栖热袍菌作为生产有价值化学品的全细胞催化底盘具有显著的潜力。
