O-2 Carrier Myoglobin Also Exhibits beta-Lactamase Activity That Is Regulated by the Heme Coordination State

Heme proteins perform a variety of biological functions and also play significant roles in the field of bio-catalysis. The beta-lactamase activity of heme proteins has rarely been reported. Herein, we found, for the first time, that myoglobin (Mb), an O-2 carrier, also exhibits novel beta-lactamase activity by catalyzing the hydrolysis of ampicillin. The catalytic proficiency ((k(cat)/K-M)/k(uncat)) was determined to be 6.25 x 10(10), which is much higher than the proficiency reported for designed metalloenzymes, although it is lower than that of natural beta-lactamases. Moreover, we found that this activity could be regulated by an engineered disulfide bond, such as Cys46-Cys61 in F46C/L61C Mb or by the addition of imidazole to directly coordinate to the heme center. These results indicate that the heme active site is responsible for the beta-lactamase activity of Mb. Therefore, the study suggests the potential of heme proteins acting as beta-lactamases, which broadens the diversity of their catalytic functions.