Francesco Mutti is associate professor of Biocatalysis at the University of Amsterdam (Netherlands). He graduated in Industrial Chemistry (2004) at the University of Milan (Italy). After obtaining his PhD in Chemistry (2008), he was research associate in the groups of Prof. Wolfgang Kroutil at the University of Graz (2009-2012) and Prof. Nicholas Turner at the University of Manchester (UK; 2013-2014). Since 2015, he is the group leader of the Biocatalysis at the University of Amsterdam. Among the others, he has been a Marie Skłodowska-Curie fellow and received an ERC Starting Grant as well as several Dutch national grants and industry funds. He has published over 55 research papers including publications in Science, Nature Catalysis, Nature Communications, JACS, Angew. Chem., Green Chem., ACS Catal., several book chapters and 5 world patents. Among the others, he is Fellow of Royal Society of Chemistry (UK) and honorary member of the Argentinian Chemical Society. His main research interest is on the development of biocatalytic cascades for the sustainable synthesis of chemicals, enzyme discovery and engineering, continuous flow biocatalysis, biocatalysis in vivo and bio-electrochemistry.

Presentation: Biocatalytic Synthesis of Chiral Amines as API intermediates

Biocatalysis is based on the use of enzymes to perform chemical conversions of organic compounds. Enzymes normally operate under mild reaction conditions and with high chemo-, regio- and stereoselectivity, thereby maximizing yield and minimizing waste generation and energy consumption. Therefore, biocatalysis is well placed to play a pivotal role in achieving the Sustainable Development Goals of the European Union and worldwide. Biocatalysis is also a high multidisciplinary field that utilizes and develops concepts and tools from bio-organic chemistry, biochemistry, molecular biology, protein engineering, bioinformatics, and computational chemistry. In this lecture, I will illustrate some of our research in biocatalytic synthesis of α-chiral amines. These molecules are important for API manufacture since ca. 40% of the optically active drugs sold on the market contain an α-chiral amine moiety or a derivative thereof (e.g., amide).For instance, my group focused on the synthesis of chiral amines from prochiral ketones using ω-transaminases (ωTAs) as well as alternative novel aminating enzymes such as amine dehydrogenases (AmDHs) and imine reductases (IReds). In this context, we have created a new family of AmDHs that was successfully applied for the synthesis of pharmaceutically relevant amines in enantiopure form. In my group, we also design and develop biocatalytic cascades that consist in the combination of several enzymes in one-pot to perform the multi-step conversion of a starting material into a final product without any intermediate isolation and purification step. This concept allows for maximizing productivity and minimizing waste generation. For instance, AmDHs, IReds and ωTAs were incorporated into biocatalytic cascades with other enzyme families to perform the conversion of alcohols, or styrene derivatives, or α-amino acids or α,β-unsaturated ketones into chiral amines, or amino alcohols containing up to two stereogenic centers and excellent stereoselectivities. One example is the biocatalytic conversion of alcohols into α-chiral amines (i.e., hydride-borrowing cascade) using alcohol dehydrogenases (ADH) and an AmDH; we developed this biotransformation using isolated enzymes, or co-immobilized enzymes, or even E. coli cells expressing the enzymes in vivo. The concept was extended to the synthesis of amino alcohols with two stereogenic centers. We also achieved efficient biocatalytic synthesis of chiral amines by using immobilized AmDHs or ωTAs in continuous flow.