21] Pathways of biosynthesis of the guanidinated inositol moieties of streptomycin and bluensomycin

Abstract

This chapter discusses the pathways of biosynthesis of the guanidinated inositol moieties of streptomycin and bluensomycin. Studies in vivo on the biosynthesis of streptomycin by intact mycelia have provided important guideposts for enzymic studies with cell-free extracts. Two analogous sequences of enzymic reactions each, operating in series, appear to be involved in biosynthesis of the streptidine moiety of dihydrostreptomycin from myo-inositol . Each sequence converts a hydroxyl group to a guanidino group and involves, in order, a dehydrogenation (C and H), transamination (D and I), phosphorylation (E and J), transamidination (F and K), and dephosphorylation (G and N). For pairs of corresponding reactions in the two sequences, it is known that different enzymes are involved, although some have overlapping substrate specificities. Knowledge concerning enzymic reactions involved in the biosynthesis and metabolism of a given antibiotic can be utilized in rational approaches to: (1) the design of fermentation media for increased antibiotic production, (2) mutant selection procedures for obtaining superior producing strains, and (3) the directed biosynthesis of structural analogs of the antibiotic.