Mutagenesis by normal metabolites in Escherichia coli: phenylalanine mutagenesis is dependent on error-prone DNA repair.

In search of a model for the production of 'spontaneous' mutations induced by DNA damage produced during normal metabolism, 19 amino acids were tested for mutagenicity in Escherichia coli K-12 uvrB. Cystine, and, to a lesser extent, arginine and threonine were found to be antimutagenic; only phenylalanine was found to be mutagenic. At 2 mM, phenylalanine induced mutants at 1.5-2-fold above background [lacZ53(amber)----Lac+, rifampicin resistance (missense), and bacteriophage T6 resistance]. Tyrosine and, to a lesser extent, tryptophan (each at 2 mM) inhibited the mutagenicity of phenylalanine. Phenylalanine mutagenesis was detected in the uvrB strain, but not in the wild-type, uvrB umuC or uvrB lexA strains. Thus, phenylalanine seems to cause the production of excisable lesions ('UV-like'?) in DNA, which, if not excised, can induce mutations via error-prone DNA repair.