2024 article
Variation in Biosynthesis and Metal-Binding Properties of Isonitrile-Containing Peptides Produced by Mycobacteria versus Streptomyces
Chen, T.-Y., Chen, J., Ruszczycky, M. W., Hilovsky, D., Hostetler, T., Liu, X., … Chang, W.-chen. (2024, March 19). ACS CATALYSIS.
author keywords: isonitriles; Fe/2OG enzymes; metallophores; Mycobacterium; natural products
UN Sustainable Development Goal Categories
3. Good Health and Well-being
(Web of Science)
Source: Web Of Science
Added: April 1, 2024
A number of bacteria are known to produce isonitrile-containing peptides (INPs) that facilitate metal transport and are important for cell survival; however, considerable structural variation is observed among INPs depending on the producing organism. While nonheme iron 2-oxoglutarate-dependent isonitrilases catalyze isonitrile formation, how the natural variation in INP structure is controlled and its implications for INP bioactivity remain open questions. Herein, total chemical synthesis is utilized with X-ray crystallographic analysis of mycobacterial isonitrilases to provide a structural model of substrate specificity that explains the longer alkyl chains observed in mycobacterial versus Streptomyces INPs. Moreover, proton NMR titration experiments demonstrate that INPs regardless of the alkyl chain length are specific for binding copper instead of zinc. These results suggest that isonitrilases may act as gatekeepers in modulating the observed biological distribution of INP structures, and this distribution may be primarily related to differing metal transport requirements among the producing strains.