8 research outputs found
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
Cyclodimerization of Mohangamide A by Thioesterase Domain Is Directed by Substrates
Mohangamide A is a pseudo-dimeric nonribosomal peptide biosynthesized along with its monomer, WS9326A, and is expected to be formed by the head-to-tail cyclodimerization of linear WS9326A and another identical peptide chain with a different acyl side chain. In vitro experiments with the N-acetylcysteamine thioesters of the corresponding monomeric intermediates and thioesterase domains of Streptomyces sp. SNMSS and S. calvus showed that this cyclodimerization reaction is directed by the substrate structures and occurs only with both linear intermediates.N
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'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