Fundamental understanding of enzymes

We are capitalizing on in silico computational toools in concert with experimental biotechnology to expand our fundamental understanding of biocatalysts and their reaction mechanisms.

Fundamental enzymology

Water fuels the chemistry of life

In the Syrén lab we are highly interested in the importance of water networks in enzymes. We believe that redesign and reconfiguration of these networks is a new engineering strategy with great potential to generate enzymes with modulated binding affinity and improved catalytic versatility. In particular in silico enzyme design is used in designing these modulated networks.

Modulating enzyme activity through stabilizing the transition state with favorable water networks.

Moreover, we are interested in understanding the evolution of proteins, which can lead to an enhanced understanding of structure-function relationships and may also be a promising strategy for enzyme engineering. We use bioinformatics methods, in particular ancestral sequence reconstruction, to learn about the evolution of enzyme characteristics.

In ancestral sequence reconstruction, sequences of putative ancestral proteins are inferred. These proteins can then be produced in bacteria and characterized in the laboratory.

Life is easy to identify, but remarkably hard to define. One fundamental property of living organisms is the order they create in their environment through evolved metabolic pathways, organized structures and self-replication which are basal energy-consuming processes dependent on enzymes that accelerate the chemistry of life up to 10^26-fold. Fundamental and organizational tasks, for instance energy conversion and information processing, would take millions – or even billions – of years in the absence of enzymes, thus representing timescales that would be incompatible with life.

The Syrén lab works with computer simulations and bioinformatics, as well as experimental biotechnology and protein engineering to enhance our fundamental understanding of enzymes, their mechanisms and evolution at the atomistic level. Towards reaching this goal we bridge fundamental chemical principles with state-of-the art biotechnology. Through transdisciplinary scientific methods we are developing novel enzyme engineering strategies for applications within biopolymer science and for the generation of superior biopharmaceuticals and fine chemicals from renewable sources.

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