The E. coli Siderophores Enterobactin and Salmochelin Form Six-Coordinate Silicon Complexes at Physiological pH

摘要

Iron is essential for nearly all organisms, because it is a key component of many metalloenzymes that catalyze redox reactions of critical importance for cellular growth. Typically, Fe~(3+) concentrations of 10~(-6)-10~(-5)m are required for growth of most bacterial species, but under aerobic conditions Fe~(3+) is not readily bioavailable because of the formation of poorly water-soluble polymeric iron aquo-hydroxo complexes. As a result, the concentration of soluble iron is as low as 10~(-10)m at pH 7.4. To extract iron from the environment, bacteria and fungi produce low-molecular-weight chelators, termed siderophores, which possess high Fe~(3+) affinity. The chelating moieties are typically catechol, hydroxamate, and carboxylate groups. Among them, enterobactin (Ent; 1), produced by E. coli and Salmonella, exhibits the highest binding constant observed thus far. In humans, iron is found in iron-binding proteins, such as transferrin and ferritin, and is a central constituent of myoglobin, hemoglobin, and P450-type mono-oxygenases. In all cases the iron complex formation constants are orders of magnitude lower than what is observed in bacterial siderophores. Consequently, protein-bound iron in humans can be extracted by siderophores which are therefore considered bacterial virulence factors.