Biosynthetic gene cluster of the non-ribosomally synthesized cyclodepsipeptide skyllamycin: deciphering unprecedented ways of unusual hydroxylation reactions

The cyclic depsipeptide skyllamycin A is a potent inhibitor of the platelet-derived growth factor (PDGF) signaling pathway by inhibiting binding of homodimeric PDGF BB to the PDGF β-receptor. Its structure contains a cinnamoyl side chain and shows a high amount of β-hydroxylated amino acids as well as an unusual α-hydroxyglycine moiety as a rare structural modification. The skyllamycin biosynthetic gene cluster was cloned and sequenced from Streptomyces sp. Acta 2897. Its analysis revealed the presence of open reading frames encoding proteins for fatty acid precursor biosynthesis, non-ribosomal peptide synthetases, regulators, and transporters along with other modifying enzymes. Specific in-frame mutagenesis of these tailoring enzymes resulted in the production of novel skyllamycin derivatives revealing that β-hydroxy groups in skyllamycin A are introduced by a promiscuous cytochrome P450 monooxygenase, whereas a two-component flavin-dependent monooxygenase is involved in α-hydroxylation.     

A Survey of Complementary Methods for the Characterization of Dense Colloidal Silica

The aim of this study is to enhance existing knowledge of different techniques developed for the characterization of stability and particle sizing of nanoparticles in dense dispersions subjected to interparticulate and hydrodynamic forces. Silica suspension, commercially known as Klebosol^® 30R50 and consisting of a particle size of 80 nm on average, was investigated in the study over a wide range of concentrations. The investigations were carried out using different optical and acoustic techniques such as laser diffraction, multiple light scattering, photon correlation spectroscopy and acoustic spectroscopy. The study details the capabilities and limitations of these modern techniques based on the different physical principles behind the characterization of the size distribution of particles in suspensions. The results are presented in terms of particle size ranges, solid concentration and technological aspects such as online and offline analysis. An important finding is that many of these modern techniques need to be improved for applications at higher concentrations since the standard models become practically invalid because of the complex interaction of acoustic and optical waves with particles in suspensions of silica.