Engineered biosynthesis of milbemycins in the avermectin high-producing strain Streptomyces avermitilis

Additional file 3 : Figure S2. HPLC analysis of milbemycins produced from S. avermitilis mutant strains and authentic standard milbemycins

Characterization of the Two Methylation Steps Involved in the Biosynthesis of Mycinose in Tylosin

The <i>S</i>-adenosyl-l-methionine-dependent <i>O</i>-methyltransferases TylE and TylF catalyze the last two methylation reactions in the tylosin biosynthetic pathway of <i>Streptomyces fradiae</i>. It has long been known that the TylE-catalyzed C2‴-<i>O</i>-methylation of the 6-deoxy-d-allose bound to demethylmacrocin or demethyllactenocin precedes the TylF-catalyzed C3‴-<i>O</i>-methylation of the d-javose (C2‴-<i>O</i>-methylated 6-deoxy-d-allose) attached to macrocin or lactenocin. This study reveals the unexpected substrate promiscuity of TylE and TylF responsible for the biosynthesis of d-mycinose (C3‴-<i>O</i>-methylated d-javose) in tylosin through the identification of a new minor intermediate 2‴-<i>O</i>-demethyldesmycosin (<b>2</b>; 3‴-methyl-demethyllactenocin), which lacks a 2‴-<i>O</i>-methyl group on the mycinose moiety of desmycosin, along with 2‴-<i>O</i>-demethyltylosin (<b>1</b>; 3‴-methyl-demethylmacrocin) that was previously detected from the <i>S. fradiae</i> mutant containing a mutation in the <i>tylE</i> gene. These results unveil the unique substrate flexibility of TylE and TylF and demonstrate their potential for the engineered biosynthesis of novel glycosylated macrolide derivatives

One-Pot Combinatorial Biosynthesis of Glycosylated Anthracyclines by Cocultivation of <i>Streptomyces</i> Strains Producing Aglycones and Nucleotide Deoxysugars

Anthracyclines, such as doxorubicin, are effective anticancer drugs composed of a tetracyclic polyketide aglycone and one or more deoxysugar moieties, which play a critical role in their biological activity. A facile one-pot combinatorial biosynthetic system was developed for the generation of a range of glycosylated derivatives of anthracyclines. Cocultivation of <i>Streptomyces venezuelae</i> mutants producing two anthracycline aglycones with eight different nucleotide deoxysugar-producing <i>S. venezuelae</i> mutants that coexpress a substrate-flexible glycosyltransferase led to the generation of 16 aklavinone or ε-rhodomycinone glycosides containing diverse deoxysugar moieties, seven of which are new. This demonstrates the potential of the one-pot combinatorial biosynthetic system based on cocultivation as a facile biological tool capable of combining diverse aglycones and deoxysugars to generate structurally diverse polyketides carrying engineered sugars for drug discovery and development

MOESM3 of Engineered biosynthesis of milbemycins in the avermectin high-producing strain Streptomyces avermitilis

Additional file 3 : Figure S2. HPLC analysis of milbemycins produced from S. avermitilis mutant strains and authentic standard milbemycins

MOESM5 of Engineered biosynthesis of milbemycins in the avermectin high-producing strain Streptomyces avermitilis

Additional file 5 : Figure S4. Sequence of inactivated aveD

Nyuzenamide C, an Antiangiogenic Epoxy Cinnamic Acid-Containing Bicyclic Peptide from a Riverine Streptomyces sp.

A new nonribosomal peptide, nyuzenamide C (1), was discovered from riverine sediment-derived Streptomyces sp. DM14. Comprehensive analysis of the spectroscopic data of nyuzenamide C (1) revealed that 1 has a bicyclic backbone composed of six common amino acid residues (Asn, Leu, Pro, Gly, Val, and Thr) and four nonproteinogenic amino acid units, including hydroxyglycine, beta-hydroxyphenylalanine, p-hydroxyphenylglycine, and 3,beta-dihydroxytyrosine, along with 1,2-epoxypropyl cinnamic acid. The absolute configuration of 1 was proposed by J-based configuration analysis, the advanced Marfey&apos;s method, quantum mechanics-based DP4 calculations, and bioinformatic analysis of its nonribosomal peptide synthetase biosynthetic gene cluster. Nyuzenamide C (1) displayed antiangiogenic activity in human umbilical vein endothelial cells and induced quinone reductase in murine Hepa-1c1c7 cells.N