Valine-sensitive acetohydroxy acid synthases in Escherichia coli K-12: Unique regulation modulated by multiple genetic sites

Spontaneous mutants (146) of Escherichia coli K-12 were selected that were resistant to inhibition of growth by 1.2 mM L-valine (Valr). The Valr isolates, containing acetohydroxy acid synthase resistant to feedback inhibition by L-valine (AHASr), were classed according to cotransduction of the mutation with leu. Several mutations resulting in an AHASr phenotype were found to be cotransducible with glyA. However, no mutations causing a Valr phenotype were linked to ilv. AHAS activity was more closely examined in representatives of three classes of mutants with Valr linked to leu, labeled ilv-660, ilv-661, and ilv-662. The ilvE503 allele in E. coli K-12, known to cause a two- to three-fold derepression of AHAS, was found to affect regulation of synthesis of both valine-sensitive AHAS (AHASs) and AHASr in the mutants containing ilv-660 and ilv-661, whereas it affected repression of AHASs, only, in the mutant containing ilv-662. Further, both AHASs and AHASr in the ilv-661 mutant were repressed by valine, whereas valine did not repress AHASr synthesis in the strain carrying ilv-660 and only partially repressed AHASr in the strain carrying ilv-662. Unexpectedly, AHASr synthesis in strains carrying ilv-660 or ilv-662 was repressible by leucine. The ilv-660 locus appears to be similar in position to ilvH and encodes a product that confers valine-sensitivity upon AHAS activity in the wild-type E. coli K-12. The ilv-660 and ilv-662 loci may normally encode products that influence both the feedback sensitivity of AHAS and control of AHAS biosynthesis.