The structure of A201A, a novel nucleoside antibiotic.

The Aminonucleoside Antibiotic A201A is Inactivated by a Phosphotransferase Activity from Streptomyces Capreolus NRRL 3817, the Producing Organism

“…In addition, a furanose found in the latter is very closely related to the unsaturated sugar of A201A (Kakinuma and Sakagami, 1978;Kirst et al, 1985). These similarities suggest that certain enzymes and, therefore, the corresponding genes of the A201A biosynthetic pathway may have related counterparts involved in puromycin and hygromycin A biosynthesis.…”

“…The assignment of the proton resonances of A201A was straightforward, on the basis of the assignments given elsewhere (Kirst et al, 1985) for the product dissolved in dry (C'H,),SO and a joint consideration of chemical shifts and coupling patterns of the different signals, which were all well resolved. When comparing the chemical shifts of A201A and the phosphorylated product in (ZHJmethanol, all resonances showed no change in their chemical shifts with the exception of those assigned to H1, H2 and H3 of the unsaturated hexofuranose moiety for which the A6 (P-A201A versus A201A) were 0.11, 0.43 and 0.25, respectively.…”

“…Streptomyces cupreolus NRRL 3817 (the A201A producer; Kirst et al, 1985), S. lividuns 66 (1326) (Hopwood et al, 1985b), Escherichiu coli DH5 (Hanahan, 1985) and TG1 (Brown, 1991) are described in the indicated references. Streptomyces-E. coli cosmid vector pJAR4 , Streptomyces vectors pIJ702 (Hopwood et al, 1985a) and pGM9 (Muth et al, 1989), and E. coli phages M13mp18 and M13mp19 (YanischPerron et al, 1985) have been described.…”

Characterization of the biosynthetic gene cluster (ata) for the A201A aminonucleoside antibiotic from Saccharothrix mutabilis subsp. capreolus

“…Two compounds were identified in the HPLC profiles of the presumed A201A-containing samples. Their retention times corresponded to those of A201A and a putative A201A molecule lacking the disaccharide moiety (probably that considered as hydrolysis product 1 by Kirst et al 5 ). The identity of these substances was confirmed by ESI-MS (Figure 2b Taken together these results indicate that the~34 kb-long S. mutabilis subsp.…”

“…4 Its chemical structure includes a moiety derived from D-rhamnose, the N 6 , N 6 -dimethyl-3ʹ-amino-3ʹ-deoxyadenosyl (aminonucleoside) moiety of puromycin, an α-methyl-p-coumaric acid (a polyketide) and an unsaturated furanose moiety closely related to similar structures found in hygromycin A (Figure 1). 5 The structural basis for both Hygromycin A and A201A antibiotics binding and inhibition to ribosomes have been recently showed by Polikanov et al 6 The similarities of A201A structure with puromycin and hygromycin A antibiotics strongly suggest that certain enzymes, and hence the corresponding genes in the A201A biosynthetic pathway, may be related to their counterparts in the puromycin and hygromycin A biosynthetic pathways. [7][8][9][10][11] Homologs of the ata open reading frames (ORFs) have indeed been found with for at least 14 ORFs of the hygromycin A biosynthetic cluster in S. hygroscopicus 9 and as we showed previously a set of five consecutive genes involved in the biosynthesis of the aminonucleoside moiety of A201A 12 and their deduced products (AtaP3, AtaP4, AtaP5, AtaP7 and AtaP10) are similar to their counterparts from the pur cluster of S. alboniger (Pur3, Pur4, Pur5, Pur7 and Pur10, respectively), genes implicated in the biosynthesis of the aminonucleoside moiety of puromycin.…”