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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
biochemistry, genetics and molecular biology
Synthetic biotechnology to study and engineer ribosomal bottromycin biosynthesis
Chemistry and Biology, Volume 19, No. 10, Year 2012
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Description
Bottromycins represent a promising class of antibiotics binding to the therapeutically unexploited A-site of the bacterial ribosome. By inhibiting translation they are active against clinically important pathogens, such as vancomycin-resistant Enterococci. Structurally, bottromycins are heavily modified peptides exhibiting various unusual biosynthetic features. To set the stage for compound modification and yield optimization, we identified the biosynthetic gene cluster, used synthetic biotechnology approaches to establish and improve heterologous production, and generated analogs by pathway genetic engineering. We unambiguously identified three radical SAM methyltransferase- encoding genes required for various methylations at unactivated carbons yielding tert-butyl valine, methyl-proline, and β-methyl-phenylalanine residues, plus a gene involved in aspartate methyl-ester formation. Evidence for the formation of the exo-thiazole unit and for a macrocyclodehydration mechanism leading to amidine ring formation is provided. © 2012 Elsevier Ltd.
Authors & Co-Authors
Huo, Liujie
Germany, Saarbrucken
Helmholtz-institut Für Pharmazeutische Forschung Saarland Hips
Rachid, Shwan Kamal
Germany, Saarbrucken
Helmholtz-institut Für Pharmazeutische Forschung Saarland Hips
Iraq, Koya
Koya University
Stadler, Marc
Germany, Braunschweig
Helmholtz Centre for Infection Research Hzi
Wenzel, Silke C.
Germany, Saarbrucken
Helmholtz-institut Für Pharmazeutische Forschung Saarland Hips
Müller, Rolf
Germany, Saarbrucken
Helmholtz-institut Für Pharmazeutische Forschung Saarland Hips
Statistics
Citations: 117
Authors: 5
Affiliations: 3
Identifiers
Doi:
10.1016/j.chembiol.2012.08.013
ISSN:
10745521
Research Areas
Genetics And Genomics