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A concise synthesis of single-enantiomer β-lactams and β-amino acids using Rhodococcus globerulus

Lloyd, Michael, Lloyd, Richard, Keene, Philip, Osborne, Andrew
Journal of chemical technology and biotechnology 2007 v.82 no.12 pp. 1099-1106
Rhodococcus globerulus, acids, amino acids, beta-lactamase, beta-lactams, biocatalysts, drugs, pharmaceutical industry, screening
BACKGROUND: Pharmaceutical companies continue to evaluate β-amino acids and β-lactams in a range of drug candidates. The development of a highly efficient and selective bioresolution of cyclic β-lactam substrates could yield enantiopure lactams and β-amino acids with medicinal potential. The aim of this work was to discover and develop a biocatalyst capable of selectively hydrolysing β-lactam substrates.RESULTS: Screening of our in-house culture collection led to the discovery of a microorganism, Rhodococcus globerulus (NCIMB 41042) with β-lactamase activity. Whole-cell bioresolutions of the β-lactams 1-4 were successfully carried out and in all cases enantiomeric excesses of the residual lactam and amino acid product were found to be greater than 98%. For one example, the bioresolution was optimised to operate at 60 g L⁻¹ substrate concentration with a 20% wt/wt cell paste loading.CONCLUSION: A microorganism, Rhodococcus globerulus (NCIMB 41042), capable of selectively hydrolysing a range of cyclic β-lactams, has been discovered. A scalable whole-cell bioresolution process has been developed, leading to the synthesis of multigram quantities of enantiomerically pure β-lactams and β-amino acids.