Rifamycin Biosynthesis Studied with 13C Enriched Precursors and Carbon Magnetic Resonance

The biosynthesis of 3-amino-5-hydroxybenzoic acid (AHBA), the precursor of mC7N units in ansamycin and mitomycin antibiotics: a review

“…3,4 This so-called mC 7 N unit was the only part of the structural core not derived from acetate/propionate units. Such mC 7 N units were also found in ansamycins of the 'benzenic' type, such as geldanamycin 5 and the maytansinoids, 6 and in the unrelated family of the mitomycin antibiotics ( Figure 1).…”

“…Preliminary enzymatic assays of this presumed RifKL complex showed NADH formation from UDP-glucose, but not dTDP-glucose, Mg 2+ and NAD + (Figure 8b). The rate of NADH formation was enhanced when glutamine was included in the incubation, NH 4 + or asparagine were 30% less effective as nitrogen donors and neither glutamate nor aspartate showed activity (Figure 8c) (Arakawa K, unpublished data). 66 Unfortunately, at this point the investigations came to an end because of the retirement of the senior investigator.…”

Studies directed towards the biosynthesis of the C7N-unit of rifamycin B: Incorporation of (14C(G))quinic acid and (1,2-13C2)glycerol.

“…1992 14C-quinic acid (5) was utilized to a large extent for the synthesis of other metabolites. The same explanation could hold for the slightly lower incorporation rate shown for P8/1-OG (8).…”

Ansamycin Biogenesis: Studies on a Novel Rifamycin Isolated from a Mutant Strain of Nocardia mediterranei

“…This precursor would have fundamentally the same carbon skeleton as the streptovaricins, and would give rise to the rifamycins by loss of a l)ropionate-derived methyl from the ansa chain and introduction of an ether linkage between the ansa and chromophore. This proposal has promptly received support from the results of [1-'3C ]propionate incorporation into streptovaricin D (10) that indicated a biosynthetic scheme for this compound identical to that independently proposed on the basis of the results obtained for rifamycin S (9).…”

“…They were the first examples of a novel class of secondary metabolites characterized by the possession of an aliphatic ansa chain bridging an aromatic chromophore, which Prelog has denominated the ansamycins (3). Members of this group so far identified can be divided into two subgroups according to the chromophore present: those containing a naphthalenic moiety [rifamycins, tolypomycins (4), and streptovaricins (5)] and those containing a benzenic moiety [maytansines (6), colubrinol (7), and geldanamycin (8) ]; representative structures are shown in Scheme 1. In a previous publication (9) describing the biosynthesis of rifamycin S, we proposed a general scheme for the biogenesis of the ansamycin carbon skeleton in which a single polyketide chain is initiated by a seven carbon amino precursor containing a six-membered ring. According to this scheme, the naphthalenic chromophore, when present, is formed by closure of a second ring including the 2nd, 3rd, and 4th carbons of the polyketide chain, e.g., C-7, C-6, and C-5 in the case of the rifamycins.…”