Enzymatic biosynthesis of β-lactam antibiotics

β-Lactam antibiotics (BLAs) are bactericidal drugs inhibiting bacterial growth by obstructing penicillin-binding proteins (PBPs) responsible for the transpeptidation/cross-linking process during cell wall biosynthesis. The β-lactam ring, a four-membered lactam, is a cyclic amide having a nitrogen atom coupled with the β-carbon of the carbonyl ring. It consists of four major classes, that is, penicillin derivatives, cephalosporins, monobactams, and carbapenems. The drugs that constitute >60% of the antimicrobials are from naturally occurring β-lactams. It represents one of the premier categories of antibiotics advised for antibacterial treatment even today after five decades of its discovery. Most of the β-lactams are produced via fermentation or modification of fermented intermediates except for carbapenems and aztreonam. The β-lactam biosynthesis generally follows nonoxidative reactions. However, enzymatic synthesis is also important by using enzymes such as 2-oxoglutarate (2OG)-dependent oxygenases, isopenicillin N synthase, clavaminic acid synthase, β-lactam synthetases, nonribosomal peptide synthetases, etc. The chapter discusses the knowledge of the enzymology leading to the biosynthesis of BLAs and their effective derivatives.