Common Principles in Macrolactone (Marginolactone) Biosynthesis. Studies on the Desertomycin Family

Abstract

Administration of sodium [13C]-labeled acetates and sodium [l-13C]propionate to cultures of Streptoverticillium baldacii subsp. netropse (strain FH-S 1625) proved the polyketide origin of the 42-membered macrolactone in oasomycin B (1), a member of the desertomycin family. In a series of feeding different amino acids as presumptive polyketide starters ornithine was found to embody the initiator of the oasomycin biosynthesis, in which oxidative deamination, decarboxylation, and CoA-activation steps are involved. Resulting from the feeding of D,L-[l-13C]glucose, the D-mannose located at C22 of 1 derives from glucose via isomerization at C2 during carbohydrate metabolism. A fermentation in an [1802]-enriched atmosphere proved the oxidative deamination reaction during the macrolactone initiation. In addition, an oxygenase introduces the OH group at C22, which is used as the connecting site for the post-polyketide mannosylation step. Consequently, the glycosylation reaction as well as other characteristics of the desertomycin family's biosynthesis illuminate unexpected analogies and common principles in the formation of a number of related macrocyclic lactones. Due to the obvious biosynthetic relationships we introduce the term "marginolactones" for this class of actinomycetes macrolactones.

Caylobolide B, a Macrolactone from Symplostatin 1-Producing Marine Cyanobacteria Phormidium spp. from Florida

“…Secondary metabolites from these organisms mainly consist of nonribosomally derived peptides and peptide−polyketide hybrids. , Pure polyketides, assembled only by polyketide synthases, represent a minor fraction of isolated compounds from the phylum Cyanobacteria. These usually polyhydroxylated compounds are reminiscent of secondary metabolites from dinoflagellates such as the cytotoxic amphidinolides, amphidinols, and luteophanols as well as bacteria-derived antibiotics desertomycins and oasomycins …”

Biosynthesis and attachment of novel bacterial polyketide synthase starter units

“…142 The biosynthetic building blocks of the marginolactone oasomycin B 54 have been determined and show that the biosynthesis of this macrolide is probably initiated by ornithine-derived 4-aminobutanoyl-CoA and chain extended in a type I PKS fashion with 12 acetate and nine propionate units (Scheme 17). 143 Labels from ornithine, aspartic acid, glutamic acid, and 4-aminobutanoic acid were all incorporated into the polyketide starter unit of 54 and desertomycin A 55. The biosynthetic relationship between the various desertomycins and oasomycins, which differ in the nature of the starter unit-derived side chain at C41, was examined by analyzing the fermentation time course.…”

Ubiquitous bacterial polyketides induce cross-kingdom microbial interactions

“…Azalomycin F is a member of the family of marginolactones whose biosynthesis starts with arginine. Marginolactones consist of a macrolactone backbone and a side chain containing a guanidyl- or amino group ( 25 ). The marginolactones desertomycin A and monazomycin are produced by Streptomyces macronensis and Streptomyces mashuensis , respectively ( 26, 27 ).…”