Zhu_2014_Bioorg.Med.Chem.Lett_24_4899

Whole cells of Bradyrhizobium japonicum USDA 6 showed both (+)-gamma-lactamase activity and (-)-gamma-lactamase activity. Insight into the genome of B. japonicum USDA 6 revealed two potential gamma-lactamases: a type I (+)-gamma-lactamase and a (-)-gamma-lactamase, making it the first strain to contain two totally different enantioselective lactamases. Both recombinant enzymes could easily be used to prepare either optically pure (+)-gamma-lactam ((+)-2-azabicyclo[2.2.1]hept-5-en-3-one) or optically pure (-)-gamma-lactam ((-)-2-azabicyclo[2.2.1]hept-5-en-3-one), which are versatile synthetic building blocks for the synthesis of various carbocyclic nucleosides and carbocyclic sugar analogues. Bioinformatic analysis showed that the type I (+)-gamma-lactamase belongs to the amidase signature family, with 504 amino acids; the (-)-gamma-lactamase, which consists of 274 amino acids, belongs to the hydrolase family. Here, we report that B. japonicum USDA contains a (-)-gamma-lactamase in addition to a (+)-gamma-lactamase, and it is the (-)-gamma-lactamase from this strain that is examined in detail in this Letter. Enzymatic synthesis of optically pure (+)-gamma-lactam with nearly 50% isolated yield and >99% ee was achieved.