Engineering small lantibiotics by use of novel enzymes and introducing additional modifications
Antibiotic resistance of human pathogens is on the rise, causing great threats to human health. Good surveillance and stewardship are needed, but not sufficient to tackle the problem. We will take lantibiotics and other modified peptides as scaffolds to design and produce novel antimicrobials with desired properties, including high activity against drug resistant pathogens such as Enterococcus faecalis, Klebsiella pneumoniae, Streptococcus pneumoniae. Selected molecules will be optimized for high stability, low rate of resistance development, good pharmacokinetic properties and low toxicity and histamine release. In the resistance development studies we will investigate the occurrence of persister and heteroresister cells, and determine the kinetics and the propensity of resistance development.
Department: Molecular Genetics, RUG
Principal investigator(s): Oscar Kuipers
Arias-Orozco, P., Inklaar, M., Lanooij, J., Cebrián, R., & Kuipers, O. P. (2021). Functional Expression and Characterization of the Highly Promiscuous Lanthipeptide Synthetase SyncM, Enabling the Production of Lanthipeptides with a Broad Range of Ring Topologies. ACS Synthetic Biology, 10(10), 2579-2591. https://doi.org/10.1021/acssynbio.1c00224
Arias-Orozco, P., Yi, Y., Kuipers, O. P., & Stewart, F. J. (2021). Draft Genome Sequences of Four Bacterial Strains of Heterotrophic Alteromonas macleodii and Marinobacter, Isolated from a Nonaxenic Culture of Two Marine Synechococcus Strains. Microbiology Resource Announcements, 10(19), e00116-00121. https://doi.org/doi:10.1128/MRA.00116-21