Pipecolic acid, a non-proteinogenic amino acid, is a metabolite in lysine metabolism and a key chiral precursor in local anesthesia and macrolide antibiotics. To replace the environmentally unfriendly chemical production or preparation procedure of pipecolic acid, many biological synthetic routes have been studied for a long time. Among them, synthesis by lysine cyclodeaminase (LCD), encoded by pipA, has several advantages, including stability of enzyme activity and NAD+ self-regeneration. Thus, we selected this enzyme for pipecolic acid biosynthesis in a whole-cell bioconversion. To construct a robust pipecolic acid production system, we investigated important conditions including expression vector, strain, culture conditions, and other reaction parameters. The most important factor was the introduction of multiple pipA genes into the whole-cell system. As a result, we produced 724 mM pipecolic acid (72.4 % conversion), and the productivity was 0.78 g/L/h from 1 M l-lysine after 5 days. This is the highest production reported to date.

中文翻译：

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通过在大肠杆菌全细胞系统中表达多种赖氨酸环脱氨酶来增强哌可酸的生产

哌可酸是一种非蛋白氨基酸，是赖氨酸代谢的代谢物，也是局部麻醉和大环内酯类抗生素的关键手性前体。长期以来，为了取代对环境不友好的哌可酸的化学生产或制备工艺，人们研究了许多生物合成路线。其中，由pipA编码的赖氨酸环脱氨酶（LCD）合成具有多种优势，包括酶活性的稳定性和NAD+的自我再生。因此，我们选择了这种酶用于全细胞生物转化中的哌啶酸生物合成。为了构建强大的哌啶酸生产系统，我们研究了重要的条件，包括表达载体、菌株、培养条件和其他反应参数。最重要的因素是将多个 pipA 基因引入全细胞系统。结果，我们生产了 724 mM 哌可酸（72.4 % 转化率），5 天后从 1 M L-赖氨酸中的生产率为 0.78 g/L/h。这是迄今为止报告的最高产量。