Effect of l-Homoserine on the Growth of Mycobacterium tuberculosis

l-Homoserine was observed to inhibit the growth of Mycobacterium tuberculosis. In the metabolism of M. tuberculosis, l-homoserine was found to be a precursor of threonine, isoleucine, and methionine. l-Homoserine-inhibited cells contained elevated levels of the enzyme acetohydroxy acid synthetase. In addition, washed cell suspensions of M. tuberculosis formed significant amounts of alpha-amino-n-butyric acid from supplements of l-homoserine. dl-Alpha-amino-n-butyric acid proved to be much more inhibitory for growth than l-homoserine. Growth antagonism by l-homoserine was reversed by l-lysine, l-threonine, and combinations of l-leucine with l-valine. At the cellular level, these amino acids reduced the amount of acetohydroxy acid synthetase in cells grown with l-homoserine and competed with dl-homoserine-4-(14)C for entrance into the extractable cell pool. l-Isoleucine also antagonized the conversion of l-homoserine to alpha-amino-n-butyric acid. Available data indicated that the effect of l-homoserine was related to its conversion to alpha-amino-n-butyric acid which subsequently inhibited growth.