Aspartate aminotransferase Rv3722c governs aspartate-dependent nitrogen metabolism in Mycobacterium tuberculosis. Academic Article uri icon

abstract

  • Gene rv3722c of Mycobacterium tuberculosis is essential for in vitro growth, and encodes a putative pyridoxal phosphate-binding protein of unknown function. Here we use metabolomic, genetic and structural approaches to show that Rv3722c is the primary aspartate aminotransferase of M. tuberculosis, and mediates an essential but underrecognized role in metabolism: nitrogen distribution. Rv3722c deficiency leads to virulence attenuation in macrophages and mice. Our results identify aspartate biosynthesis and nitrogen distribution as potential species-selective drug targets in M. tuberculosis.

published proceedings

  • Nat Commun

altmetric score

  • 16.8

author list (cited authors)

  • Jansen, R. S., Mandyoli, L., Hughes, R., Wakabayashi, S., Pinkham, J. T., Selbach, B., ... Rhee, K. Y.

citation count

  • 29

complete list of authors

  • Jansen, Robert S||Mandyoli, Lungelo||Hughes, Ryan||Wakabayashi, Shoko||Pinkham, Jessica T||Selbach, Bruna||Guinn, Kristine M||Rubin, Eric J||Sacchettini, James C||Rhee, Kyu Y

publication date

  • April 2020