Schmitt, Steven and Montalban-Lopez, Manuel and Peterhoff, David and Deng, Jingjing and Wagner, Ralf and Held, Martin and Kuipers, Oscar P. and Panke, Sven (2019) Analysis of modular bioengineered antimicrobial lanthipeptides at nanoliter scale. NATURE CHEMICAL BIOLOGY, 15 (5). 437-+. ISSN 1552-4450, 1552-4469
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The rise of antibiotic resistance demands the acceleration of molecular diversification strategies to inspire new chemical entities for antibiotic medicines. We report here on the large-scale engineering of ribosomally synthesized and post-translationally modified antimicrobial peptides carrying the ring-forming amino acid lanthionine. New-to-nature variants featuring distinct properties were obtained by combinatorial shuffling of peptide modules derived from 12 natural antimicrobial lanthipeptides and processing by a promiscuous post-translational modification machinery. For experimental characterization, we developed the nanoFleming, a miniaturized and parallelized high-throughput inhibition assay. On the basis of a hit set of >100 molecules, we identified variants with improved activity against pathogenic bacteria and shifted activity profiles, and extrapolated design guidelines that will simplify the identification of peptide-based anti-infectives in the future.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NATURAL-PRODUCTS; PEPTIDE; NISIN; BIOSYNTHESIS; LANTIBIOTICS; PROTEIN; LEADER; PROMISCUITY; MACHINERY; PLATFORM; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Apr 2020 06:24 |
| Last Modified: | 15 Apr 2020 06:24 |
| URI: | https://pred.uni-regensburg.de/id/eprint/27120 |
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