Total synthesis of methymycin.

Co-produced natural ketolides methymycin and pikromycin inhibit bacterial growth by preventing synthesis of a limited number of proteins

Antibiotics methymycin (MTM) and pikromycin (PKM), co-produced by Streptomyces venezuelae, represent minimalist macrolide protein synthesis inhibitors. Unlike other macrolides, which carry several side chains, a single desosamine sugar is attached to the macrolactone ring of MTM and PKM. In addition, the macrolactone scaffold of MTM is smaller than in other macrolides. The unusual structure of ...

Title: APPROACHES TO THE SYNTHESIS OF METHYMYCIN

Several approaches to the synthesis of methymycin were investigated. Segment A (39), containing functionality corresponding to C-9, 10, and 11 of methynolide was made in six steps from propionaldehyde in an overall yield of 37%. Oxidation of 34 with silver nitrate gave 35 which, upon hydroxylation with hydrogen peroxide, gave the erythro isomer of dihydroxy acid 36. This acid was resolved with ...

Synthesis of Macrolide Antibiotics. IV. Stereoselective Syntheses of the 3-0-Methyl and the 11-0-Methyl Derivatives of the C(1)-C(6) Segment of Erythrono1ides A and B and the C(9)-C(15) Segment of Erythronolide A, Respectively.tf

By appropriate dissection of the macrocyclic lactone ring of methymycin erythromycins A and B, picromycin and narbomycin, carbohydrate-like structural segments were obtained. The finding that the anomeric configuration of a glycopyranoside effectively controls the stereochemistry of various addition reactions to sp' (C=O and C=C) carbon atoms of a glycopranoside ring led to the development of a...

Complete Genome Sequence of Streptomyces venezuelae ATCC 15439, Producer of the Methymycin/Pikromycin Family of Macrolide Antibiotics, Using PacBio Technology

Here, we report the complete genome sequence of Streptomyces venezuelae ATCC 15439, a producer of the methymycin/pikromycin family of macrolide antibiotics and a model host for natural product studies, obtained exclusively using PacBio sequencing technology. The 9.03-Mbp genome harbors 8,775 genes and 11 polyketide and nonribosomal peptide natural product gene clusters.

Chain elongation, macrolactonization, and hydrolysis of natural and reduced hexaketide substrates by the picromycin/methymycin polyketide synthase.