Institute for Bioengineering, School of Engineering, University of Edinburgh, Faraday Building, King's Buildings, Colin Maclaurin Road, Edinburgh, EH9 3DW, UK.
School of Chemistry, University of St. Andrews, Purdie Building, North Haugh, St. Andrews, KY16 9ST, UK.
Chembiochem. 2020 Jul 1;21(13):1856-1860. doi: 10.1002/cbic.202000051. Epub 2020 Mar 3.
Selectively fluorinated compounds are found frequently in pharmaceutical and agrochemical products where currently 25-30 % of optimised compounds emerge from development containing at least one fluorine atom. There are many methods for the site-specific introduction of fluorine, but all are chemical and they often use environmentally challenging reagents. Biochemical processes for C-F bond formation are attractive, but they are extremely rare. In this work, the fluorinase enzyme, originally identified from the actinomycete bacterium Streptomyces cattleya, is engineered into Escherichia coli in such a manner that the organism is able to produce 5'-fluorodeoxyadenosine (5'-FDA) from S-adenosyl-l-methionine (SAM) and fluoride in live E. coli cells. Success required the introduction of a SAM transporter and deletion of the endogenous fluoride efflux capacity in order to generate an E. coli host that has the potential for future engineering of more elaborate fluorometabolites.
在医药和农用化学品产品中，经常会发现选择性氟化化合物，目前有 25-30%经过优化的化合物在开发中脱颖而出，其中至少含有一个氟原子。有许多方法可用于特定位置的氟原子引入，但都是化学方法，而且它们通常使用对环境具有挑战性的试剂。形成 C-F 键的生化过程很有吸引力，但却极为罕见。在这项工作中，氟酶原酶最初是从放线菌链霉菌属卡特利雅中鉴定出来的，经过工程改造后被导入到大肠杆菌中，使该生物体能够在活的大肠杆菌细胞中由 S-腺苷甲硫氨酸 (SAM) 和氟化物生成 5'-氟脱氧腺苷 (5'-FDA)。为了生成一个具有未来工程化更复杂氟代代谢物潜力的大肠杆菌宿主，成功需要引入一个 SAM 转运蛋白，并删除内源性氟化物外排能力。
