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Theme 2 colloquium by dr. Clemens Mayer: 'Repurposing natural designs for man-made innovations' (Lecture)

Date
Tuesday 9 March 2021Add to my calendar
Time
from 16:00
Location
zoom
Speaker
dr. Clemens Mayer (Stratingh Institute for Chemistry, University of Groningen)
Description

Our understanding of the complex, molecular processes in living organisms is at a level that seemed unimaginable only decades ago. Courtesy of the efforts that enabled this unprecedented insight, we have access to a powerful arsenal of tools that makes chemists and biologists uniquely equipped to become engineers and facilitate man-made innovations. Pursuing this enticing concept, this lecture will discuss our group’s efforts to chemically upgrade (1) cellular factories that enable the production of value-added molecules and (2) peptide libraries to identify new lead compounds for therapeutic interventions.

We envision cellular factories as entities, in which synthetic catalysts perform new-to-nature transformations on molecules, which are provided by biocatalysts in designer microbes. However, it has proven challenging to identify synthetic catalysts that can function in concert with cells and develop strategies that enable us to engineer enzymes in microbes that produce compounds of no apparent value for an organism. To meet these challenges, we create biosensors that enable both the discovery of biocompatible small-molecule catalysts and the optimization of biotechnologically-relevant enzymes.[1][2] These biosensors are based on the incorporation of non-canonical amino acids into proteins that give rise to a selectable phenotype, such as an optical readout or survival.

In a second research line, we aim to mimic the chemogenetic optimization strategies nature has employed to evolve bioactive compounds. For example, macrocyclic peptides (MPs), such as the antibiotic vancomycin, are the result of evolutionary algorithms that fine-tuned both the amino acids sequence as well as posttranslational processes for cyclizations or the introduction of non-peptidic moieties. We mimic such natural products by developing strategies for the generation and selection of chemically-upgraded MPs. For the upgrade, we employ modified privileged scaffolds – those are common building blocks for constructing small-molecule libraries – as non-peptidic cyclization units on the surface of bacteriophages.[3] This strategy enables us to generate billions of natural-product-like MPs simultaneously and select binders that combine favorable traits of small-molecule and peptide-based drugs by phage display.

[1] R. Rubini, I. Ivanov & C. Mayer, Chemistry – A European Journal, 2019, 25, 16017-16021
[2] R. Rubini & C. Mayer, ACS Chemical Biology, 2020, 15, 12, 3093–3098
[3] T.R. Oppewal, J. Hekelaar & C. Mayer, ChemRxiv, https://doi.org/10.26434/chemrxiv.13705618.v1

Contact
dr. Peter Korevaar & dr. Evan Spruijt
Register

Please see the announcement sent by  email or contact the organizers.