Biological glycosidation of macrolide aglycones. I. Isolation and characterization of 5-O-mycaminosyl narbonolide and 9-dihydro-5-O-mycaminosyl narbonolide.

Abstract

Glycosidation of narbonolide with mycaminose was attempted by feeding narbonolide during the fermentation of a parent or a mutant strain of Streptomyces platensis, a producer of 16-membered macrolide antibiotics, platenomycins.As a result, two new compounds I and II were isolated from the fermentation broth and identified as 5-0-mycaminosyl narbonolide (I) and 9-dihydro-5-O-mycaminosyl narbonolide (II), respectively. Physicochemical and antimicrobial properties of I and II are also referred to.Hitherto, a number of aglycones of macrolide antibiotics have been isolated,'-') and used for the elucidation of the biosynthetic pathway of this antibiotic group, e.g. erythromycin,') picromycin') and platenomycins.11)As reported previously, the authors isolated narbonolide, the aglycone of narbomycin, from the culture of Streptomyces venezuelae MCRL-0376 which produced narbomycin and picromycin as major antibiotics, '','') and succeeded in the bioconversion of biologically inactive narbonolide into active antibiotics (narbomycin and picromycin) by glycosidation of the aglycone.9)In 1972, rosamicin was reported") to consist of an aglycone identical with that of cirramycin AI and a sugar which was identified as desosamine. Considering that rosamicin is constructed from a 16-membered aglycone and a sugar usually found in 12-or 14-membered macrolide antibiotics, it was conversely assumed that a new antibiotic might be obtained by combining a sugar normally present in 16-membered macrolide antibiotics with a 14-membered macrolide aglycone.Thus, glycosidation of narbonolide with mycaminose (a sugar component of 16-membered macrolide antibiotics, such as platenomycin, leucomycin, spiramycin, cirramycin, tylosin, carbomycin etc.) was attempted by adding narbonolide during the fermentation of platenomycin-producing Streptomyces platensis MCRL-0388141 and its blocked mutant (strain U-21). Two new compounds I and II were successfully derived from narbonolide.In this paper, the isolation and characterization of these biotransformed compounds I and II as 5-0-mycaminosyl narbonolide and 9-dihydro-5-O-mycaminosyl narbonolide respectively is described. Microorganism and FermentationThe strains employed in this investigation were Streptomyces platensis subsp. malvinus MCRL-0388, a producer of the platenomycins and a mutant strain U-21. Strain U-21 was derived by treatment of the parent strain with ultraviolet irradiation. Strain U-21 was completly blocked in an early stage of platenomycin biosynthesis and unable to synthesize the antibiotics de novo. However, this

An automated Genomes-to-Natural Products platform (GNP) for the discovery of modular natural products

“…3d ). Potensimicin appears similar to mycaminose-modified narbonolide compounds that have been observed previously 41 42 , and shares similar bioactivity profiles ( Supplementary Table 14 ).…”

A comprehensive review of glycosylated bacterial natural products

“…Additional sugars attached to C-5 include 3-keto-4,6-dideoxy-β-D-hexopyranose 179 (CP-63693 640 ), β-D-chalcose ( 181b ; lankamycins 659 and kujimycins 654 ) and β-D-mycaminose ( 185 ; narbolide, 663 via biotransformation). C-6 substitution is restricted to α-L-megosamine ( 45 ; megalomycin 656 and SF2748 664 ) while that of C-9 is limited to variants of α-L-rhamnose ( 14–18 ; lyngbyaloside and lyngbuilloside 665,666 ).…”

“…Additional C-3-appended sugars observed include 4′- O -acetyl-α- l -arcanose ( 122b ) [and corresponding engineered 2′,3′-anhydro-arcanose ( 182 ) and 3′-acetylated 180 657,658 ] of the lankamycins 659 and the kujimycins [which contain a C-3 α- l -arcanose ( 122a ) or 4′- O -acetyl-α- l -arcanose ( 122b ) and a C-5 β- d -lankavose ( 181b )] 660 and α- l -oleandrose ( 184 ); found in oleandomycin 647,661 and the 3- O -oleandrosyl-5- O -desosaminyl-(8 S )-8-hydroxyerythronolide B 662 from bioconversion. Additional sugars attached to C-5 include 3-keto-4,6-dideoxy-β- d -hexopyranose 179 (CP-63693 640 ), β- d -chalcose ( 181b ; lankamycins 659 and kujimycins 654 ) and β- d -mycaminose ( 185 ; narbolide, 663 via biotransformation). C-6 substitution is restricted to α- l -megosamine ( 45 ; megalomycin 656 and SF2748 664 ) while that of C-9 is limited to variants of α- l -rhamnose ( 14–18 ; lyngbyaloside and lyngbuilloside 665,666 ).…”

New erythromycin derivatives from Saccharopolyspora erythraea using sugar O‐methyltransferases from the spinosyn biosynthetic gene cluster

“…Additional encouragement for such experiments comes, however, from a substantial body of previous experiments on the production of hybrid macrolides by bioconversion, in which the macrolactone served as the heterologous partner. Thus, feeding of a mutant strain of Streptomyces platensis , blocked at an early stage in the biosynthetic pathway to the 16‐membered macrolide platenomycin, with the 14‐membered macrolactone narbonolide led to the production of 5‐O‐mycaminosylnarbonolide (Maezawa et al ., 1976). Similarly, 6‐deoxyerythronolide B can serve as a substrate for the late steps in oleandomycin biosynthesis (Spagnoli et al ., 1983), and protylonolide, the aglycone of the 16‐membered macrolide tylosin, has been converted successfully into so‐called chimeramycins by the action of a spiramycin‐producing strain, Streptomyces ambofaciens , in the presence of cerulenin to block aglycone production (Omura et al ., 1983).…”