Department of Industrial Microbiology and Biotechnology, State Key Laboratory of Mycology, Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China.
School of Life Sciences, Yunnan University, Kunming 650500, China.
J Agric Food Chem. 2024 Mar 27;72(12):6500-6508. doi: 10.1021/acs.jafc.4c00003. Epub 2024 Mar 12.
Dipicolinic acid (DPA), a cyclic diacid, has garnered significant interest due to its potential applications in antimicrobial agents, antioxidants, chelating reagents, and polymer precursors. However, its natural bioproduction is limited since DPA is only accumulated in Bacillus and Clostridium species during sporulation. Thus, heterologous production by engineered strains is of paramount importance for developing a sustainable biological route for DPA production. KT2440 has emerged as a promising host for the production of various chemicals thanks to its robustness, metabolic versatility, and genetic tractability. The dominant Entner-Doudoroff (ED) pathway for glucose metabolism in this strain offers an ideal route for DPA production due to the advantage of NADPH generation and the naturally balanced flux between glyceraldehyde-3-phosphate and pyruvate, which are both precursors for DPA synthesis. In this study, DPA production via the ED pathway was designed in KT2440. The systematically engineered strain produced dipicolinate with a titer of 11.72 g/L from glucose in a 5 L fermentor. This approach not only provides a sustainable green route for DPA production but also expands our understanding of the metabolic potential of the ED pathway in KT2440.
二吡咯烷二羧酸（DPA）是一种环状二羧酸，由于其在抗菌剂、抗氧化剂、螯合剂和聚合物前体等方面的潜在应用而备受关注。然而，由于 DPA 仅在芽孢杆菌和梭菌属物种的孢子形成过程中积累，因此其天然生物生产受到限制。因此，通过工程菌株进行异源生产对于开发 DPA 生产的可持续生物途径至关重要。
KT2440 因其稳健性、代谢多样性和遗传可操作性而成为生产各种化学品的有前途的宿主。该菌株中葡萄糖代谢的主导 Entner-Doudoroff（ED）途径为 DPA 生产提供了理想的途径，因为它有利于 NADPH 的生成，并且甘油醛-3-磷酸和丙酮酸之间的通量自然平衡，这两者都是 DPA 合成的前体。在本研究中，通过 ED 途径在 KT2440 中设计了 DPA 生产。经过系统工程改造的菌株在 5 L 发酵罐中从葡萄糖生产出 11.72 g/L 的二吡咯烷二酸盐。这种方法不仅为 DPA 的生产提供了可持续的绿色途径，而且扩展了我们对 ED 途径在 KT2440 中的代谢潜力的理解。
