Researchers:
Jun Yan, Meng Bi, Allen K. Bourdon, Abigail T. Farmer, Po-Hsiang Wang, Olivia Molenda, Andrew T. Qualie, Nannan Jiang, Yi Yang, Yongchao Yin, Burcu Şimşir, Shawn R. Campagna, Elizabeth A. Edwards, Frank E. Löffler
Abstract:
Cobamides such as vitamin B12 are structurally conserved, cobalt-containing tetrapyrrole biomolecules that have essential biochemical functions in all domains of life. In organohalide respiration, a vital biological process for the global cycling of natural and anthropogenic organohalogens, cobamides are the requisite prosthetic groups for carbon–halogen bond-cleaving reductive dehalogenases. This study reports the biosynthesis of a new cobamide with unsubstituted purine as the lower base and assigns unsubstituted purine a biological function by demonstrating that Coα-purinyl-cobamide (purinyl-Cba) is the native prosthetic group in catalytically active tetrachloroethene reductive dehalogenases of Desulfitobacterium hafniense. Cobamides featuring different lower bases are not functionally equivalent, and purinyl-Cba elicits different physiological responses in corrinoid-auxotrophic, organohalide-respiring bacteria. Given that cobamide-dependent enzymes catalyze key steps in essential metabolic pathways, the discovery of a novel cobamide structure and the realization that lower bases can effectively modulate enzyme activities generate opportunities to manipulate functionalities of microbiomes.
Citation:
Yan J, Bi M, Bourdon AK, Farmer AT, Wang P-H, Molenda O, Quaile AT, Jiang N, Yang Y, Yin Y, Şimşir B, Campagna SR, Edwards EA, Löffler FE. 2017. Purinyl-cobamide is a native prosthetic group of reductive dehalogenases. Nature Chemical Biology, 10.1038/nchembio.2512.
