Tylosin polyketide synthase module 3: stereospecificity, stereoselectivity and steady-state kinetic analysis of β-processing domains via diffusible, synthetic substrates.

Tylosin polyketide synthase module 3: stereospecificity, stereoselectivity and steady-state kinetic analysis of β-processing domains via diffusible, synthetic substrates† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c5sc01505g Click here for additional data file.

Conserved amino acid residues correlating with ketoreductase stereospecificity in modular polyketide synthases.

Table 1 classifies the KR domains in the PKSs reviewed in [4] and the amphotericin PKS. Fig. 4 shows the ClustalW-generated alignments of A and B-type KR domains. A-type KRs are above the gap, B-type below. In fatty acid and polyketide biosynthesis, dehydration of a β-hydroxyacyl chain normally forms a trans double bond. Fig. 5 shows alignments of the 88-103 region and the 134-149 region in KR ...

Polyketide Intermediate Mimics as Probes for Revealing Cryptic Stereochemistry of Ketoreductase Domains

Among natural product families, polyketides have shown the most promise for combinatorial biosynthesis of natural product-like libraries. Though recent research in the area has provided many mechanistic revelations, a basic-level understanding of kinetic and substrate tolerability is still needed before the full potential of combinatorial biosynthesis can be realized. We have developed a novel ...

Genetic analysis of polyketide synthase and peptide synthase genes of ‎cyanobacteria as a mining tool for new pharmaceutical compounds

Cyanobacteria are considered a promising source for new ‎pharmaceutical lead compounds and a large number of chemically diverse and ‎bioactive metabolites have been obtained from cyanobacteria. Despite of ‎several worldwide studies on prevalence of NRPSs and PKSs among the ‎cyanobacteria, none of them included Iranian cyanobacteria of Kermanshah ‎province. Therefore, the aim of this study was t...

Substrate Controlled Divergence in Polyketide Synthase Catalysis

Biochemical characterization of polyketide synthases (PKSs) has relied on synthetic substrates functionalized as electrophilic esters to acylate the enzyme and initiate the catalytic cycle. In these efforts, N-acetylcysteamine thioesters have typically been employed for in vitro studies of full PKS modules as well as excised domains. However, substrate engineering approaches to control the cata...