Summary auto-generated
This study investigates the genetic control of histidine biosynthetic enzymes in Salmonella typhimurium by analyzing enzyme levels in various histidine-requiring mutants. The researchers identified four key enzymes in the final steps of histidine biosynthesis and correlated specific mutant classes with deficiencies in individual enzymes: B mutants lack imidazoleglycerol phosphate dehydrase, C mutants lack imidazoleacetol phosphate transaminase, and D mutants lack histidinol dehydrogenase. By growing histidine-requiring mutants on N-α-formyl-L-histidine instead of excess histidine, the researchers achieved approximately 15-fold increases in enzyme levels, facilitating enzyme detection and quantification. The linear arrangement of genes on the bacterial chromosome (F, A, B, C, D) corresponds to the sequential order of enzymes in the biosynthetic pathway, demonstrating that gene organization reflects metabolic pathway organization. Additionally, multisite deletion mutants lacking multiple genes were found to lack multiple enzymes, confirming the functional linkage of these genes in histidine biosynthesis.
Key findings
- Gene classes B, C, and D control specific histidine biosynthetic enzymes: dehydrase, transaminase, and dehydrogenase respectively
- The linear order of genes on the bacterial chromosome (F-A-B-C-D) corresponds to the sequential order of enzyme reactions in the histidine biosynthetic pathway
- Growing histidine-requiring mutants on formylhistidine instead of excess histidine increases enzyme levels approximately 15-fold, enabling more sensitive enzyme detection
- Multisite mutations affecting multiple genes result in deficiencies of multiple enzymes, demonstrating functional linkage of biosynthetic genes
- Gene repression by the end-product histidine can be overcome by limiting histidine availability during growth
This summary was generated automatically from the article PDF and is not part of the original publication. Refer to the PDF for the authoritative text.
Abstract
SUMMARY: The last four enzymes in the pathway of L-histidine biosynthesis have been assayed in various histidineless mutants of Salmonella typhimurium. Three classes of mutants (B, C and D) have been shown to be associated with lack of imidazoleglycerol phosphate dehydrase, imidazoleacetol phosphate transaminase, and histidinol dehydrogenase, respectively. These studies, in conjunction with the genetic work of Hartman, Loper & erman (1960), indicate that the sequence of the genes on the chromosome corresponds to the sequence of the enzymes in the pathway of the biosynthesis. Certain mutants, which were shown genetically to behave as multisite mutants, have been shown to be missing these three enzymes. These multisite mutants are also missing a fourth biosynthetic enzyme, histidinol phosphate phosphatase, for which no single site mutants are available. It has been found that the level of activity of the series of enzymes of histidine biosynthesis can be raised about 15-fold over the wild-type level by growing a histidine-requiring mutant on formylhistidine as a source of histidine.