D-Glucosamine and L-citrulline, precursors in mitomycin biosynthesis by Streptomyces verticillatus

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

“…7 A number of other compounds also seemed to contain mC 7 N units, such as validamycin 8 and acarbose, 9 pactamycin, 10 as well as asukamycin 11 and the manumycins, 12 and were proposed to have a similar biosynthetic origin. 11,13 However, subsequent work has shown their origins to be different. The mC 7 N unit of validamycin and acarbose arises from 2-epi-5-epi-valiolone, a product of the cyclization of seduheptulose 7-phosphate, 14 that of pactamycin from the shikimate pathway via 3-aminobenzoic acid, 15 and those of asukamycin and manumycin from 3-amino-4-hydroxybenzoic acid, which arises from the condensation of a triose phosphate and a C 4 -dicarboxylic acid.…”

“…The mC 7 N unit of validamycin and acarbose arises from 2-epi-5-epi-valiolone, a product of the cyclization of seduheptulose 7-phosphate, 14 that of pactamycin from the shikimate pathway via 3-aminobenzoic acid, 15 and those of asukamycin and manumycin from 3-amino-4-hydroxybenzoic acid, which arises from the condensation of a triose phosphate and a C 4 -dicarboxylic acid. 16 The incorporation patterns of labeled precursors into several ansamycins and into mitomycins, 13,[17][18][19] as well as mutant complementation studies 20 all suggested a shikimate pathway origin of the mC 7 N unit, but attempts to incorporate labeled shikimic acid, quinic acid or 3-dehydroquinic acid were unsuccessful. 17,19,[21][22][23] The nonincorporation of shikimic acid could be because of permeability barriers.…”

“…However, it is also involved in the biosynthesis of other compound classes, as exemplified by the mitomycins and FR900482, in which it is combined with an aminosugar as the second component. 13,35,68 Other examples are the tetrapetalones, 38 which were shown to incorporate an AHBA moiety, and diazepinomicin, which was also proposed to incorporate an AHBA-derived moiety, although final proof is still outstanding. 69 A particularly intriguing example are the saliniketals from Salinispora arenicola, which share a biosynthetic pathway with the rifamycins.…”

Structural studies of mitomycins. I. Absolute configurations of mitomycins A and B

“…Their results are not necessarily consistent with the configurations determined by X-ray analysis, o-Glucosamine is incorporated into mitomycins efficiently (incorporation rate of 2.3%) by Streptomyces verticillatus and provides its C6 unit of C1, C2, C3, C9a, C9 and C10 and the N atom of the aziridine ring without any cleavage of C-C and C-N bonds of the amino sugar during biosynthesis (Hornemann et al, 1974). On the other hand, incorporation rates of L-glucosamine and omannosamine, both with the same configuration at C2 as determined by X-rays, are 0.6% and less than 0.01%, respectively.…”

“…Studies of the biosynthesis of mitomycins have been carried out by Hornemann and co-workers (Hornemann, Kehrer, Nunez & Ranieri, 1974;Hornemann & Aikman, 1973). Their results are not necessarily consistent with the configurations determined by X-ray analysis, o-Glucosamine is incorporated into mitomycins efficiently (incorporation rate of 2.3%) by Streptomyces verticillatus and provides its C6 unit of C1, C2, C3, C9a, C9 and C10 and the N atom of the aziridine ring without any cleavage of C-C and C-N bonds of the amino sugar during biosynthesis (Hornemann et al, 1974).…”