Glyoxylate detoxification is an essential function of malate synthase required for carbon assimilation in Mycobacterium tuberculosis

• DOI: 10.1073/pnas.1617655114
• Publication Date: 2017-03-07T02:00:34Z
• Authors: Susan Puckett; Carolina Trujillo; Zhe Wang; Hyungjin Eoh; Thomas R. Ioerger; Inna Krieger; James Sacchettini; Dirk Schnappinger; Kyu Y. Rhee; Sabine Ehrt
• Keywords: Malate synthase; Assimilation (phonology); Detoxification; Coenzyme A

Significance A better understanding of essential processes in Mycobacterium tuberculosis ( Mtb ) is required for the development new chemotherapeutics. Isocitrate lyase (ICL) and malate synthase (MS) function glyoxylate shunt, a pathway by to metabolize fatty acids (FAs). Here, we demonstrate that MS enables growth survival on through its ability simultaneously detoxify metabolic byproduct arising from initial assimilation acetyl coenzyme (acetyl-CoA), glyoxylate, while assimilating second molecule acetyl-CoA. We further show depletion during acute chronic mouse infections kills . These studies expand our fundamental shunt biologically validate as an attractive drug target