Liu Wei, Yuan Shan, Jin Miaomiao, Xian Mo
CAS Key Laboratory of Biobased Materials, Qingdao Institute of Bioenergy and Bioprocess Technology, Chinese Academy of Sciences, Shandong, China.
University of Chinese Academy of Sciences, Beijing, China.
Front Bioeng Biotechnol. 2022 Aug 17;10:969012. doi: 10.3389/fbioe.2022.969012. eCollection 2022.
Fluorine has become an important element for the design of synthetic molecules for use in medicine, agriculture, and materials. The introduction of fluorine atoms into organic compound molecules can often give these compounds new functions and make them have better performance. Despite the many advantages provided by fluorine for tuning key molecular properties, it is rarely found in natural metabolism. We seek to expand the molecular space available for discovery through the development of new biosynthetic strategies that cross synthetic with natural compounds. Towards this goal, 2-fluoro-3-hydroxypropionic acid (2-F-3-HP) was first synthesized using coexpressing methylmalonyl CoA synthase (MatBrp), methylmalonyl CoA reductase (MCR) and malonate transmembrane protein (MadLM). The concentration of 2-F-3-HP reached 50.0 mg/L by whole-cell transformation after 24 h. 2-F-3-HP can be used as the substrate to synthesize other fluorides, such as poly (2-fluoro-3-hydroxypropionic acid) (FP3HP). Being entirely biocatalytic, our procedure provides considerable advantages in terms of environmental and safety impacts over reported chemical methods.
氟已成为用于医学、农业和材料领域的合成分子设计中的一种重要元素。将氟原子引入有机化合物分子中通常可赋予这些化合物新的功能，并使其具有更好的性能。尽管氟在调节关键分子特性方面具有诸多优势，但在自然代谢中却很少发现。我们试图通过开发将合成化合物与天然化合物相结合的新生物合成策略，来扩大可用于发现的分子空间。为实现这一目标，首先通过共表达甲基丙二酰辅酶A合酶（MatBrp）、甲基丙二酰辅酶A还原酶（MCR）和丙二酸跨膜蛋白（MadLM）合成了2-氟-3-羟基丙酸（2-F-3-HP）。全细胞转化24小时后，2-F-3-HP的浓度达到50.0mg/L。2-F-3-HP可用作合成其他氟化物的底物，如聚（2-氟-3-羟基丙酸）（FP3HP）。我们的方法完全是生物催化的，在环境和安全影响方面比已报道的化学方法具有相当大的优势。
