Grant: Discovery Launch Supplement

Enzymes are the catalysts that nature uses to produce the chemicals it needs. Chemists working in the field of biocatalysis borrow these catalysts to use them as a greener, less polluting, cheaper, and more selective alternative to classical synthesis. As such, enzyme technology can be developed to help us solve many of the societal problems that the world is facing today. Enzymes are perfect at carrying out the metabolic reactions for which they evolved, but not necessarily the chemical reactions we want to use them for. Thanks to advancements in enzyme engineering, scientists are now able to modify said enzymes to be applicable to our specific needs. Bringing an enzyme from discovery to application, however, remains challenging due to the different nature of each enzyme (different structure, type of catalysis, cofactor dependency, growth and activity conditions, stability, promiscuity, dynamics, and more) and the difficulty with working with complex biological systems. Because of this, as it stands, every laboratory sees the engineering of an enzyme as a stand-alone problem, resulting in long times from discovery to application and rarely generating workflows that others can use. These global challenges carry huge potential for innovation, and they can be tackled systematically through standardization and automation to make enzyme technology more accessible. With this program, I want to set the basis for the development of a workflow to harness the potential of enzymes more efficiently and, therefore, rapidly to develop robust bio-based solutions to make a real/applied impact on urgent societal threats, with a focus on environmental ones. Our program focuses on: (i) the development of methods for better selection of the initial enzyme candidates, (ii) the use of synthetic biology-oriented solutions for the standardization of molecular biology `parts' from a gene assembly and mutagenesis perspective,  (iii) the use of automation for better reproducibility and high-throughput, (iv) a multifactorial approach to address the intrinsic different conditions of growth and activity of enzymes more efficiently, and (v) the use of predictive AI-powered abilities to increase predictability in the mutation of enzymes.  While working towards establishing our workflow, we will focus on solving real/applied environmental issues. In particular, (I) through an enzymatic cascade where engineered enzymes work in sequence, we will develop a biocatalytic, greener, and more sustainable alternative to the production of fragrances and flavors; (II) with a focus on the degradation of PU (polyurethane), we will discover and engineer new and efficient enzymes for plastic degradation (polyesterases and polyurethanases), a topic of great urgency today. Our work will impact the field of enzyme technology from every perspective, making it more accessible to all.