Molecular features of bile salt hydrolases and relevance in human health.

BACKGROUND: Bile salt hydrolase (BSH) enzyme is responsible for the de-conjugation of bile salts by commensal bacteria, thus playing a vital role in their colonization and survival in the mammalian intestine and determination of their probiotic potential. Further, bile deconjugation also leads to lowering of cholesterol and alterations in energy homeostasis, thus making BSH a clinically important enzyme. SCOPE OF THE REVIEW: Many recent observations have indicated that BSH may be involved in a multifaceted array of roles, directly or indirectly in the host and microbial physiology. BSH paralogues have now been found to occur in different microbes including free-living and pathogenic bacteria and Archaea. BSHs from various sources also show differential activity and substrate spectrum. Certain bacteria are known to possess multiple genes for BSH enzymes. BSHs have been reported to influence different metabolic phenomena, including bacterial pathogenesis and the maintenance of lipid and glucose homeostasis in the host. These observations necessitate an intense study into the biochemical, structural and regulatory features of BSH enzymes to better understand their role in regulating bacterial and host metabolism. MAJOR CONCLUSIONS: In this review, the available information on the characteristics of BSH enzymes have been organized in order to understand their interactions with a wide range of substrates and their myriad physiological roles, from bile resistance to signalling mechanisms. GENERAL SIGNIFICANCE: A detailed exploration of BSH architecture and regulation could provide insights into its evolution and a deeper appreciation of the multiple functions of this enzyme relevant to healthcare.

Penicillin acylases revisited: importance beyond their industrial utility.

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.