Decarboxylases and Dehydrogenases in Biocatalysis: Sustainable Production of Amines in Batch and Continuous Flow Systems

Nowadays the urgent need for sustainable and greener production processes is driving considerable interest towards the continuously progressing field of biocatalysis. Enzymes, the essential components of biocatalysis, provide an environmentally friendly approach to chemical transformations, presenting cleaner and more selective synthesis pathways compared to conventional, potentially hazardous, chemical methods. However, to truly unlock the potential of enzymes and apply them effectively at an industrial level, a great level of optimization is often required. This research introduces a set of biocatalytic tools specifically tailored to overcome the challenges associated with chemical amine production. The explored approach was the decarboxylation of natural amino acids. These precursors represent a sustainable feedstock source since they can be obtained via microbial fermentation in a circular economy, from natural and readily available substrates. The aim is to propose a green, eco-conscious alternative to traditional amine production, which often involves the generation of waste and the use of dangerous reagents. The practicality and efficiency of these novel biocatalytic instruments are validated through direct application, thereby showcasing their potential for implementation in industry. A significant aspect of the study revolves around not just the development of these biocatalytic tools, but also enhancing their resilience for industrial scale-up. The central strategy to augment the robustness of the biocatalysts, and thereby widen their application field, is the immobilization of the biocatalyst. By doing so, the biocatalyst can be integrated in an easier manner inside the chemical synthesis and can become a reliable co-actor, addressing the most environmentally problematic steps in the chemical process. This collaborative method allows biocatalysts to complement traditional chemical stages, providing an inclusive and comprehensive strategy for sustainable chemical production. Moreover, it is essential to note that the versatility of enzymes should be explored further. Out-of-the-box applications for these biological catalysts must be considered, keeping in mind that enzymatic reactions often occur under equilibrium, hence influencing the reaction directionality. In this study, an effort was made to harness the capabilities of amino acid dehydrogenases and amine dehydrogenase to catalyse the oxidative deamination reaction expanding their substrate scope. The aim is to generate aldehydes or ketones from amines, which hold promising potential in the field of chemical applications

Combined chemoenzymatic strategy for sustainable continuous synthesis of the natural product hordenine

To improve sustainability, safety and cost-efficiency of synthetic methodologies, biocatalysis can be a helpful ally. In this work, a novel chemoenzymatic stategy ensures the rapid synthesis of hordenine, a valuable phenolic phytochemical under mild working conditions. In a two-step cascade, the immobilized tyrosine decarboxylase from Lactobacillus brevis (LbTDC) is here coupled with the chemical reductive amination of tyramine. Starting from the abundant and cost-effective amino acid L-tyrosine, the complete conversion to hordenine is achieved in less than 5 minutes residence time in a fully-automated continuous flow system. Compared to the metal-catalyzed N,N-dimethylation of tyramine, this biocatalytic approach reduces the process environmental impact and improves its STY to 2.68 g/(L·h)

Flow chemistry Set-up Enables Integration of Chemo- and Biocatalysis

The move towards sustainable syntheses is a widespread effort which sees academia and industry developing new strategies and solutions. Flow chemistry, and in general the flow set up, with the compartmentalization of different steps in dedicated reactors, offers new possibility to integrate biocatalytic steps within a chemical cascade, often without the need to redesign the whole pathway. Here we report key examples in the field over the past few years

Use of FCC-NMRD relaxometry for early detection and characterization of ex-vivo murine breast cancer

We acknowledge COST Action AC15209 (EURELAX) for scientific support. This project has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 668119 (project “IDentIFY”). The Italian Ministry for Education and Research (MIUR) is gratefully aknowledged for yearly FOE funding to the Euro-BioImaging Multi-Modal Molecular Imaging Italian Node (MMMI). E.D.G. and G.F. gratefully acknowledge FIRC-AIRC (Fondazione Italiana per la Ricerca sul Cancro AIRC) for their fellowships. We gratefully acknowledge Lionel Broche for the interesting discussion about mathematical models and procedures for the fitting of NMRD data.Peer reviewedPublisher PD