Penicillin acylases revisited: importance beyond their industrial utility

Abstract

It is of great importance to study the physiological roles of enzymes in nature; however, in some cases, it is not easily apparent. Penicillin acylases are pharmaceutically important enzymes that cleave the acyl side chains of penicillins, thus paving the way for production of newer semi-synthetic antibiotics. They are classified according to the type of penicillin (G or V) that they preferentially hydrolyze. Penicillin acylases are also used in the resolution of racemic mixtures and peptide synthesis. However, it is rather unfortunate that the focus on the use of penicillin acylases for industrial applications has stolen the spotlight from the study of the importance of these enzymes in natural metabolism. The penicillin acylases, so far characterized from different organisms, show differences in their structural nature and substrate spectrum. These enzymes are also closely related to the bacterial signalling phenomenon, quorum sensing, as detailed in this review. This review details studies on biochemical and structural characteristics of recently discovered penicillin acylases. We also attempt to organize the available insights into the possible in vivo role of penicillin acylases and related enzymes and emphasize the need to refocus research efforts in this direction.

Structural analysis of a penicillin V acylase from Pectobacterium atrosepticum confirms the importance of two Trp residues for activity and specificity

“…An analysis of PVAs and Ntn hydrolases in general (Avinash et al, 2014) illuminates the distinctive quality of the family of enzymes to maintain the catalytic abb a fold even in the absence of appreciable sequence homology. A few important amino acids responsible for the catalysis (including N-terminal nucleophile and residues involved in oxyanion hole formation) are strictly conserved, thus preserving the reaction mechanism.…”

Penicillin V acylases from gram-negative bacteria degrade N-acylhomoserine lactones and attenuate virulence in Pseudomonas aeruginosa

“…PVAs occur in a diverse range of bacteria and some fungi (Avinash et al 2016b), and are usually expressed constitutively. It has been demonstrated in V. cholerae (Kovacikova et al 2003) that the PVA expression is reduced during the induction of virulence genes by the AHL-based AphA/HapR QS system and expressed more at high cell densities.…”

“…A new AHL acylase from P. aeruginosa (HacB) (Wahjudi et al 2011) cleaves Pen V to a small extent; however, AHL degradation by PVA enzymes or any other cys-Ntn hydrolase has not been explored in detail so far. Moreover, the role of PVAs in microbial physiology is not been clearly understood till date, but a few possible links to quorum sensing and pathogenesis have been suggested (Avinash et al 2016b).…”

Novel Bifunctional Acylase from Actinoplanes utahensis: A Versatile Enzyme to Synthesize Antimicrobial Compounds and Use in Quorum Quenching Processes

“…A separate cluster is formed by the cholylglycine hydrolase (CGH) group, together with the amidase group. CGH group includes PVAs and bile salt hydrolases (BSHs), having significant sequence, structural and catalytic mechanism similarities [ 49 ]. Though, the acylases Slac1 and Slac2 located in this last group have shown AHL acylase activity, whereas they are inactive on CGH substrates, β-lactam antibiotics, or bile salts [ 50 ].…”