Synthesis of Chrysobactin and its Analogues for Studying Iron Uptake System in Soft Rot Bacteria

Dickeya dadantii and Pectobacterium carotovorum are the two major plant pathogens which cause soft rot disease on a wide variety of economic important vegetables and ornamental corps around the globe. The losses cause by this kind of disease is tremendous every year. Still, there is currently no effective chemical agent against this disease. During the infection period, these soft rot bacteria secrete a small molecule iron chelator termed siderophore to scavenge iron from its host. The ability of siderophore to shuttle iron into cytoplasm of bacteria provides an ideal pathway for the Trojan horse design of siderophore-drug conjugate. The main siderophore of these soft rot bacteria – chrysobactin is a relatively weak iron chelator compared with other siderophore system. Its iron complex-receptor interaction has not been well studied. In this work we synthesized a series of chrysobactin analogues in order to study the structure-activity relationship of the chrysobactin iron complex. A new siderophore, cyclic tri-chrysobactin, reported in 2011 was also synthesized in this work. It is the cyclic form of three chrysobactin linked by ester bonds. The highly resemblance between this cyclic trimer and computational modeling of tris(chrysobactin) complex make us wonder the stoichiometric ratio of the biologically active chrysobactin complex. By chemical engineering of the trimeric chrysobactin, we successfully deliver the trimeric conjugates into its native producer, but not those who use chrysobactin. The implication of a new receptor responsible for cyclic trimer still needs to be confirmed in the future.