The ability of microorganisms, representative of a wide array of recognized genera, to utilize phenylalanine, tyrosine, phenylacetic acid and related compounds as carbon sources for growth will be established by a broad systematic survey. The sequences of enzymic reactions employed by different microbial groups for the dissimilation of these compounds will be investigated by thorough identification of intermediates and by study of individual reactions. The objectives of these investigations are to identify reaction pathways alternative to those previously described and to study individual enzyme-catalyzed reactions of fundamental importance and clinical significance. Accordingly establishment of substrate-product stoichiometry, coenzyme requirements and other parameters will follow. Enzymes which play important roles in these reaction sequences will be purified for study of their properties, specificity and mechanism of action as appropriate. Attention will be paid to the possible use of such enzymes for replacement therapy in the treatment of genetic diseases related to phenylalanine and tyrosine metabolism and for the assay of metabolites of clinical interest. Studies of the regulation of synthesis of these catabolic enzymes in selected strains will be undertaken as sensitive enzyme assays are developed and as suitable mutants are isolated. Where possible such studies will be initiated in microbial systems for which established techniques for genetic study are available.