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Properties and applications of microbial D-amino acid oxidases: current state and perspectives

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Abstract

D-Amino acid oxidase (DAAO) is a biotechnologically relevant enzyme that is used in a variety of applications. DAAO is a flavine adenine dinucleotide-containing flavoenzyme that catalyzes the oxidative deamination of D-isomer of uncharged aliphatic, aromatic, and polar amino acids yielding the corresponding imino acid (which hydrolyzes spontaneously to the α-keto acid and ammonia) and hydrogen peroxide. This enzymatic activity is produced by few bacteria and by most eukaryotic organisms. In the past few years, DAAO from mammals has been the subject of a large number of investigations, becoming a model for the dehydrogenase-oxidase class of flavoproteins. However, DAAO from microorganisms show properties that render them more suitable for the biotechnological applications, such as a high level of protein expression (as native and recombinant protein), a high turnover number, and a tight binding of the coenzyme. Some important DAAO-producing microorganisms include Trigonopsis variabilis, Rhodotorula gracilis, and Fusarium solani. The aim of this paper is to provide an overview of the main biotechnological applications of DAAO (ranging from biocatalysis to convert cephalosporin C into 7-amino cephalosporanic acid to gene therapy for tumor treatment) and to illustrate the advantages of using the microbial DAAOs, employing both the native and the improved DAAO variants obtained by enzyme engineering.

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Acknowledgements

This work was supported by grants from FAR to G. Molla, M. S. Pilone, and L. Pollegioni and from Fondazione CARIPLO to L. Pollegioni. We apologize to those whose work we were unable to cite owing to space limitations.

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  1. Department of Biotechnology and Molecular Sciences, University of Insubria, via J.H. Dunant 3, 21100, Varese, Italy

    Loredano Pollegioni, Gianluca Molla, Silvia Sacchi, Elena Rosini & Mirella S. Pilone

  2. Antibioticos S.P.A., Strada Rivoltana Km 6–7, Rodano, Italy

    Roberto Verga

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  1. Loredano Pollegioni
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  2. Gianluca Molla
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  3. Silvia Sacchi
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  4. Elena Rosini
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  6. Mirella S. Pilone
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Correspondence to Loredano Pollegioni.

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Pollegioni, L., Molla, G., Sacchi, S. et al. Properties and applications of microbial D-amino acid oxidases: current state and perspectives. Appl Microbiol Biotechnol 78, 1–16 (2008). https://doi.org/10.1007/s00253-007-1282-4

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  • DOI: https://doi.org/10.1007/s00253-007-1282-4

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