5. de Carvalho LP, Zhao H, Dickinson CE, Arango NM, Lima CD, Fischer SM, Ouerfelli O,
Nathan C, Rhee KY (2010) Activity-based
metabolomic profiling of enzymatic function:
identification of rv1248c as a mycobacterial
2-hydroxy-3-oxoadipate synthase. Chem Biol
17(4):323–332
6. Larrouy-Maumus G, Biswas T, Hunt DM,
Kelly G, Tsodikov OV, de Carvalho LP
(2013) Discovery of a glycerol 3-phosphate
phosphatase reveals glycerophospholipid polar
head recycling in mycobacterium tuberculosis.
Proc Natl Acad Sci U S A 110
(28):11320–11325
7. de Carvalho LP, Fischer SM, Marrero J,
Nathan C, Ehrt S, Rhee KY (2010) Metabolomics of mycobacterium tuberculosis reveals
compartmentalized co-catabolism of carbon
substrates. Chem Biol 17(10):1122–1131
8. Eoh H, Rhee KY (2013) Multifunctional
essentiality of succinate metabolism in adaptation to hypoxia in mycobacterium tuberculosis.
Proc Natl Acad Sci U S A 110(16):6554–6559
9. Marrero J, Rhee KY, Schnappinger D, Pethe K,
Ehrt S (2010) Gluconeogenic carbon flow of
tricarboxylic acid cycle intermediates is critical
for mycobacterium tuberculosis to establish
and maintain infection. Proc Natl Acad Sci U
S A 107(21):9819–9824
10. Marrero J, Trujillo C, Rhee KY, Ehrt S (2013)
Glucose phosphorylation is required for mycobacterium tuberculosis persistence in mice.
PLoS Pathog 9(1):e1003116
11. Eoh H, Rhee KY (2014) Methylcitrate cycle
defines the bactericidal essentiality of isocitrate
lyase for survival of mycobacterium tuberculosis on fatty acids. Proc Natl Acad Sci U S A 111
(13):4976–4981
12. Ganapathy U, Marrero J, Calhoun S, Eoh H,
de Carvalho LP, Rhee K, Ehrt S (2015) Two
enzymes with redundant fructose bisphosphatase activity sustain gluconeogenesis and virulence in Mycobacterium tuberculosis. Nat
Commun 6(1):1–12
13. Maksymiuk C, Balakrishnan A, Bryk R, Rhee
KY, Nathan CF (2015) E1 of alphaketoglutarate dehydrogenase defends Mycobacterium tuberculosis against glutamate anaplerosis and nitroxidative stress. Proc Natl Acad Sci
U S A 112(43):E5834–E5843
14. Noy T, Vergnolle O, Hartman TE, Rhee KY,
Jacobs WR, Berney M, Blanchard JS (2016)
Central role of pyruvate kinase in carbon
co-catabolism of Mycobacterium tuberculosis. J
Biol Chem 291(13):7060–7069
15. Warrier T, Kapilashrami K, Argyrou A, Ioerger
TR, Little D, Murphy KC, Nandakumar M,
Park S, Gold B, Mi J, Zhang T, Meiler E,
Rees M, Somersan-Karakaya S, Porras-De
Francisco E, Martinez-Hoyos M, BurnsHuang K, Roberts J, Ling Y, Rhee KY,
Mendoza-Losana A, Luo M, Nathan CF
(2016) N-methylation of a bactericidal compound as a resistance mechanism in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A
113(31):E4523–E4530
16. Eoh H, Wang Z, Layre E, Rath P, Morris R,
Moody DB, Rhee KY (2017) Metabolic anticipation in Mycobacterium tuberculosis. Nat
Microbiol 2(8):17084
17. Puckett S, Trujillo C, Wang Z, Eoh H, Ioerger
TR, Krieger I, Sacchettini J, Schnappinger D,
Rhee KY, Ehrt S (2017) Glyoxylate detoxification is an essential function of malate synthase
required for carbon assimilation in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A
114(11):E2225–E2232
18. Ruecker N, Jansen R, Trujillo C, Puckett S,
Jayachandran P, Piroli GG, Frizzell N,
Molina H, Rhee KY, Ehrt S (2017) Fumarase
deficiency causes protein and metabolite succination and intoxicates Mycobacterium tuberculosis. Cell Chem Biol 24(3):306–315
19. Chakraborty S, Gruber T, Barry CE 3rd, Boshoff HI, Rhee KY (2013) Para-aminosalicylic
acid acts as an alternative substrate of folate
metabolism in mycobacterium tuberculosis.
Science 339(6115):88–91
20. Kwon YK, Higgins MB, Rabinowitz JD (2010)
Antifolate-induced depletion of intracellular
glycine and purines inhibits thymineless death
in E. coli. ACS Chem Biol 5(8):787–795
21. Kwon YK, Lu W, Melamud E, Khanam N,
Bognar A, Rabinowitz JD (2008) A domino
effect in antifolate drug action in Escherichia
coli. Nat Chem Biol 4(10):602–608
22. Bockman MR, Kalinda AS, Petrelli R, De la
Mora-Rey T, Tiwari D, Liu F, Dawadi S,
Nandakumar M, Rhee KY, Schnappinger D,
Finzel BC, Aldrich CC (2015) Targeting Mycobacterium tuberculosis biotin protein ligase
(MtBPL) with nucleoside-based bisubstrate
adenylation inhibitors. J Med Chem 58
(18):7349–7369
23. Park Y, Pacitto A, Bayliss T, Cleghorn LAT,
Wang Z, Hartman T, Arora K, Ioerger TR,
Sacchettini J, Rizzi M, Donini S, Blundell TL,
Ascher DB, Rhee K, Breda A, Zhou N,
Dartois V, Jonnala SR, Via LE, Mizrahi V,
Epemolu O, Stojanovski L, Simeons F,
Osuna-Cabello M, Ellis L, MacKenzie CJ,
592
Kyle A. Planck and Kyu Rhee
Nathan C, Rhee KY (2010) Activity-based
metabolomic profiling of enzymatic function:
identification of rv1248c as a mycobacterial
2-hydroxy-3-oxoadipate synthase. Chem Biol
17(4):323–332
6. Larrouy-Maumus G, Biswas T, Hunt DM,
Kelly G, Tsodikov OV, de Carvalho LP
(2013) Discovery of a glycerol 3-phosphate
phosphatase reveals glycerophospholipid polar
head recycling in mycobacterium tuberculosis.
Proc Natl Acad Sci U S A 110
(28):11320–11325
7. de Carvalho LP, Fischer SM, Marrero J,
Nathan C, Ehrt S, Rhee KY (2010) Metabolomics of mycobacterium tuberculosis reveals
compartmentalized co-catabolism of carbon
substrates. Chem Biol 17(10):1122–1131
8. Eoh H, Rhee KY (2013) Multifunctional
essentiality of succinate metabolism in adaptation to hypoxia in mycobacterium tuberculosis.
Proc Natl Acad Sci U S A 110(16):6554–6559
9. Marrero J, Rhee KY, Schnappinger D, Pethe K,
Ehrt S (2010) Gluconeogenic carbon flow of
tricarboxylic acid cycle intermediates is critical
for mycobacterium tuberculosis to establish
and maintain infection. Proc Natl Acad Sci U
S A 107(21):9819–9824
10. Marrero J, Trujillo C, Rhee KY, Ehrt S (2013)
Glucose phosphorylation is required for mycobacterium tuberculosis persistence in mice.
PLoS Pathog 9(1):e1003116
11. Eoh H, Rhee KY (2014) Methylcitrate cycle
defines the bactericidal essentiality of isocitrate
lyase for survival of mycobacterium tuberculosis on fatty acids. Proc Natl Acad Sci U S A 111
(13):4976–4981
12. Ganapathy U, Marrero J, Calhoun S, Eoh H,
de Carvalho LP, Rhee K, Ehrt S (2015) Two
enzymes with redundant fructose bisphosphatase activity sustain gluconeogenesis and virulence in Mycobacterium tuberculosis. Nat
Commun 6(1):1–12
13. Maksymiuk C, Balakrishnan A, Bryk R, Rhee
KY, Nathan CF (2015) E1 of alphaketoglutarate dehydrogenase defends Mycobacterium tuberculosis against glutamate anaplerosis and nitroxidative stress. Proc Natl Acad Sci
U S A 112(43):E5834–E5843
14. Noy T, Vergnolle O, Hartman TE, Rhee KY,
Jacobs WR, Berney M, Blanchard JS (2016)
Central role of pyruvate kinase in carbon
co-catabolism of Mycobacterium tuberculosis. J
Biol Chem 291(13):7060–7069
15. Warrier T, Kapilashrami K, Argyrou A, Ioerger
TR, Little D, Murphy KC, Nandakumar M,
Park S, Gold B, Mi J, Zhang T, Meiler E,
Rees M, Somersan-Karakaya S, Porras-De
Francisco E, Martinez-Hoyos M, BurnsHuang K, Roberts J, Ling Y, Rhee KY,
Mendoza-Losana A, Luo M, Nathan CF
(2016) N-methylation of a bactericidal compound as a resistance mechanism in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A
113(31):E4523–E4530
16. Eoh H, Wang Z, Layre E, Rath P, Morris R,
Moody DB, Rhee KY (2017) Metabolic anticipation in Mycobacterium tuberculosis. Nat
Microbiol 2(8):17084
17. Puckett S, Trujillo C, Wang Z, Eoh H, Ioerger
TR, Krieger I, Sacchettini J, Schnappinger D,
Rhee KY, Ehrt S (2017) Glyoxylate detoxification is an essential function of malate synthase
required for carbon assimilation in Mycobacterium tuberculosis. Proc Natl Acad Sci U S A
114(11):E2225–E2232
18. Ruecker N, Jansen R, Trujillo C, Puckett S,
Jayachandran P, Piroli GG, Frizzell N,
Molina H, Rhee KY, Ehrt S (2017) Fumarase
deficiency causes protein and metabolite succination and intoxicates Mycobacterium tuberculosis. Cell Chem Biol 24(3):306–315
19. Chakraborty S, Gruber T, Barry CE 3rd, Boshoff HI, Rhee KY (2013) Para-aminosalicylic
acid acts as an alternative substrate of folate
metabolism in mycobacterium tuberculosis.
Science 339(6115):88–91
20. Kwon YK, Higgins MB, Rabinowitz JD (2010)
Antifolate-induced depletion of intracellular
glycine and purines inhibits thymineless death
in E. coli. ACS Chem Biol 5(8):787–795
21. Kwon YK, Lu W, Melamud E, Khanam N,
Bognar A, Rabinowitz JD (2008) A domino
effect in antifolate drug action in Escherichia
coli. Nat Chem Biol 4(10):602–608
22. Bockman MR, Kalinda AS, Petrelli R, De la
Mora-Rey T, Tiwari D, Liu F, Dawadi S,
Nandakumar M, Rhee KY, Schnappinger D,
Finzel BC, Aldrich CC (2015) Targeting Mycobacterium tuberculosis biotin protein ligase
(MtBPL) with nucleoside-based bisubstrate
adenylation inhibitors. J Med Chem 58
(18):7349–7369
23. Park Y, Pacitto A, Bayliss T, Cleghorn LAT,
Wang Z, Hartman T, Arora K, Ioerger TR,
Sacchettini J, Rizzi M, Donini S, Blundell TL,
Ascher DB, Rhee K, Breda A, Zhou N,
Dartois V, Jonnala SR, Via LE, Mizrahi V,
Epemolu O, Stojanovski L, Simeons F,
Osuna-Cabello M, Ellis L, MacKenzie CJ,
592
Kyle A. Planck and Kyu Rhee