Sulfonyl urea resistance is due to mutation in:
Acetolactate synthase also called acetohydroxyacid synthase catalyzes first common step of branched-chain amino acid biosynthesis: condensation of two pyruvate molecules to acetolactate leading to valine and leucine, and condensation of pyruvate and 2-ketobutyrate to acetohydroxybutyrate leading to isoleucine. Sulfonylurea herbicides such as chlorsulfuron and tribenuron bind in substrate access channel of ALS, blocking access to catalytic site containing thiamine pyrophosphate. Resistance evolves via non-synonymous mutations in ALS gene altering herbicide binding pocket without abolishing catalytic residues. Classic mutations include Pro197 to Ser, Leu, Arg, Trp and Trp574 to Leu conferring cross-resistance to multiple ALS inhibitor classes including imidazolinones. Engineered crops express mutated ALS from tobacco or Arabidopsis as selectable marker and agronomic trait. Mechanism exemplifies target-site resistance where single amino acid substitution reduces herbicide affinity, preserving amino acid synthesis under otherwise lethal herbicide doses applied for weed management. Molecular basis of sulfonylurea resistance studied via heterologous expression of mutated ALS in Escherichia coli showing retains catalytic activity for acetolactate synthesis but 1000-fold reduced herbicide binding. Residue Pro197 located in herbicide binding tunnel near catalytic center, mutation to Ser enlarges pocket reducing interaction. Commercial traits like Clearfield wheat developed through EMS mutagenesis selecting Pro197 mutants. Understanding ALS mutation mechanism
Ref: LaRossa Trends Biotech 1984 ALS mutation; Tranel Weed Sci 2002 ALS Pro197; NCBI NBK21601; PubMed 14769484 sulfonylurea resistance mechanism review.