Ansamycins, Mitomycins, and Pactamycin

Ansamycins, Mitomycins, and Pactamycin.—At last, the nature of the long-sought C7N intermediate [thickened bonds in (86), (87), and (88)1 in the biosynthesis of the ansamycins [e.g. actamycin (86) and rifamycin B (87)1, of the mitomycins [e.g. porfiromycin (88)J, and of related metabolites is known It is 3-amino-5-hydroxybenzoic acid (91). 

Independent evidence has been obtained that 3-amino-5-hydroxybenzoic acid 

The evidence then is that, for rifamycin and other ansamycins, biosynthesis diverts at a so-far unidentified (but early) compound in the shikimic acid pathway to give 3-amino-5-hydroxybenzoic acid (91) (as its CoA ester). This compound then yields, on the one hand, the mitomycins [e.g. porfiromycin (88)1 and, on the other, the CoA ester of P8/1-OG (92), which then affords diverse metabolites such as rifamycin B (87) and actamycin (86) (cf. ref. 83 for a detailed scheme). 

Protorifamycin I is the main product of cultures of N. mediterranei and a probable early intermediate in the biosynthesis of rifamycins cf. Vol. 10, p. 29). Other, related, rifamycins have also been isolated from cultures of this organism.85 

The thiazorifamycins P (94), Q (95), and Verde (96) have been shown to derive from rifamycin S (93) and cysteine.86 The formation of (94) and (96) appears to be the result only of chemical reactions, whereas the formation of (95) requires enzymic assistance. 

---