Glyoxylate detoxification is an essential function of malate synthase required for carbon assimilation in Mycobacterium tuberculosis
Malate synthase
Assimilation (phonology)
Detoxification
Coenzyme A
DOI:
10.1073/pnas.1617655114
Publication Date:
2017-03-07T02:00:34Z
AUTHORS (10)
ABSTRACT
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
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