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Therapeutics have evolved significantly over the past few decades, expanding from traditional small molecules to innovative modalities such as peptides, non-antibody based proteins, and advanced cell therapies. Accompanying this trend, enzymes are also increasingly being employed to perform complex chemical transformations with enhanced selectivity and specificity in the process to manufacture small molecule drug substances, all while promoting sustainability. All these advancements necessitate the development of scalable and robust process for the production of diverse biomolecules.

In the Process R&D Enabling Technologies group at Merck, a Novel Expression Systems team has recently been established to identify the most suitable hosts for the engineering and expression and of various biomolecules. They are exploring Bacillus subtilis and Komagataella phaffii (previously known as Pichia pastoris) as promising hosts that capitalize on the advantages of protein secretion. In this presentation, Dr. Zhen Ma, Director of Novel Expression Systems, will share preliminary findings demonstrating the successful production of a variety of target proteins in these hosts, including enzymes, peptides, and antibody derived molecules, with results achieved in bench-scale bioreactors. By closely collaborating with other internal partner groups, the ultimate goal is to enhance the understanding and efficiency throughout the DBTL (Design, Build, Test, Learn) cycle to achieve successful right-first-time scale-up and manufacturing.

Speaker

• Zhen Ma, PhD, Director, Novel Expression Systems, Zhen earned his bachelor’s degree in Biological Sciences from Fudan University, and obtained his PhD degree in the lab of Prof. David Giedroc at Texas A&M University. His PhD research focused on protein biochemistry, protein-ligand interactions and allosteric regulation. He then carried out a post-doctoral fellowship at Cornell with Prof. John Helmann in the area of Bacillus subtilis genetics and physiology. He began his professional career at Dupont Nutrition & Biosciences (now part of IFF â€� International Flavors & Fragrances) working on improving the expression of difficult-to-express proteins and industrial enzymes. Working with various expression hosts, he successfully led the straining engineering effort to commercialize multiple products. Prior to joining Merck, he managed a new Biotransformation group in the global R&D organization of Ingredion to deliver innovative solutions for food ingredients. In his current role, Zhen leads the Novel Expression Systems group, focusing on enabling and enhancing the production of diverse biomolecules to support the discovery and development of therapeutics.