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A recent update on the use of microbial transglutaminase for the generation of biotherapeutics

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Abstract

The recent scientific progresses on the use of enzyme–mediated reactions in organic, non-aqueous and aqueous media have significantly supported the growing demand of new biotechnological and/or pharmacological products. Today, a plethora of microbial enzymes, used as biocatalysts, are available. Among these, microbial transglutaminases (MTGs) are broadly used for their ability to catalyse the formation of an isopeptide bond between the γ-amide group of glutamines and the ε-amino group of lysine. Due to their promiscuity towards primary amine-containing substrates and the more stringent specificity for glutamine-containing peptide sequences, several combined approaches can be tailored for different settings, making MTGs very attractive catalysts for generating protein–protein and protein small molecule’s conjugates. The present review offers a recent update on the modifications attainable by MTG-catalysed bioreactions as reported between 2014 and 2019. In particular, we present a detailed and comparative overview on the MTG-based methods for proteins and antibodies engineering, with a particular outlook on the synthesis of homogeneous antibody–drug conjugates.

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Acknowledgements

Authors acknowledge the support from: (i) Ministero della Salute for the “Research Project on CAR T cells for hematological malignancies and solid tumors” Regione Campania for the projects: (ii) “Fighting Cancer resistance: Multidisciplinary integrated Platform for a technological Innovative Approach to Oncotherapies (Campania Oncotherapies)”; (iii) “Development of novel therapeutic approaches for treatment-resistant neoplastic diseases (SATIN)”; (iv) NANOCAN, NANOfotonica per la lotta al CANcro. Also, support from MIUR for project PRIN no 20155ACHBN to AS and 2015783N45 to MR is gratefully acknowledged. Authors also acknowledge the technical advice and support from Maurizio Amendola and Leopoldo Zona.

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Correspondence to N. Doti or M. Ruvo.

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The authors declare no conflicts of interests.

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Doti, N., Caporale, A., Monti, A. et al. A recent update on the use of microbial transglutaminase for the generation of biotherapeutics. World J Microbiol Biotechnol 36, 53 (2020). https://doi.org/10.1007/s11274-020-02829-y

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  • DOI: https://doi.org/10.1007/s11274-020-02829-y

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