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About us Practical matters How to find us C. (Clemens) Mayer, PhD

Research interests

Evolution is an autonomous, all-purpose problem solver. In nature, employing recursive cycles of diversification, selection and amplification has resulted in a plethora of biomolecules with remarkable functions. My group aspires to employ the Darwinian algorithm in the laboratory and employ selections for the creation of made-to-order biomolecules and to obtain a molecular understanding of the underlying evolutionary processes. In our efforts, make use of innovative molecular evolution approaches to:

(1) process catalytic information in bacteria to engineer efficient biocatalysts and map their structure-function relationships

(2) interface synthetic chemistry with phage display protocols to select natural-product-like macrocyclic peptides that combine the favorable traits of small-molecule and peptide-based drugs.

In a first step toward these goals, we have established an in vivo selection strategy that can elicit biotechnologically-relevant biocatalysts with vastly improved activities through serial passaging of populations harboring enzyme libraries. Requiring minimal human intervention and no specialized equipment, our strategy lends itself readily to automation and parallelization, thus making it ideal to efficiently navigate a complex sequence space. For the generation and selection of natural-product-like macrocyclic peptides, we have developed strategies to employ modified privileged scaffolds – common building blocks for small-molecule libraries – as non-peptidic cyclization units on the surface of bacteriophages. These strategies enable us to simultaneously generate billions of natural-product-like compounds that fall into a previously inaccessible chemical space, and select high-affinity binders from these libraries by phage display.

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A Robust Growth-Based Selection Platform to Evolve an Enzyme via Dependency on Noncanonical Tyrosine Analogues

Selecting Better Biocatalysts by Complementing Recoded Bacteria**

Tethered Ribosomes: Toward the Synthesis of Nonproteinogenic Polymers in Bacteria

A Strategy to Select Macrocyclic Peptides Featuring Asymmetric Molecular Scaffolds as Cyclization Units by Phage Display

Opportunities for interfacing organometallic catalysts with cellular metabolism

Catalytic and structural properties of ATP-dependent caprolactamase from Pseudomonas jessenii

Addicting Escherichia coli to New-to-Nature Reactions

Affinity-Selected Bicyclic Peptide G-Quadruplex Ligands Mimic a Protein-like Binding Mechanism

Chance emergence of catalytic activity and promiscuity in a self-replicator

Genetic-Code-Expansion Strategies for Vaccine Development

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