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Identification Of A Metabolic Disposal Route For The Oncometabolite S-(2-Succino)Cysteine In Bacillus Subtilis, Thomas D. Niehaus, Jacob Folz, Donald R. Mccarty, Arthur Cooper, David Moraga Amador, Oliver Fiehn, Andrew D. Hanson

NYMC Faculty Publications

Cellular thiols such as cysteine spontaneously and readily react with the respiratory intermediate fumarate, resulting in the formation of stable S-(2-succino)-adducts. Fumarate-mediated succination of thiols increases in certain tumors and in response to glucotoxicity associated with diabetes. Therefore, S-(2-succino)-adducts such as S-(2-succino)cysteine (2SC) are considered oncometabolites and biomarkers for human disease. No disposal routes for S-(2-succino)-compounds have been reported prior to this study. Here, we show that Bacillus subtilis metabolizes 2SC to cysteine using a pathway encoded by the yxe operon. The first step is N-acetylation of 2SC followed by an oxygenation that we propose results in the release of …