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Publication Abstract from PubMed

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 non-heme 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 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.

Variation in biosynthesis and metal-binding properties of isonitrile-containing peptides produced by Mycobacteria versus Streptomyces.,Chen TY, Chen J, Ruszczycky MW, Hilovsky D, Hostetler T, Liu X, Zhou J, Chang WC ACS Catal. 2024 Apr 5;14(7):4975-4983. doi: 10.1021/acscatal.4c00645. Epub 2024 , Mar 19. PMID:38895101^[2]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.