Site directed mutations of the C-methyltransferase domain of squalestatin tetraketide synthase were made in an attempt to alter the methylation pattern of the synthase expressed in vivo: mutation resulted in either no effect or in complete abrogation of polyketide production.

Applying directed evolution to the phloroglucinol synthase PhlD from Pseudomonas fluorescens Pf-5 has provided the first example of engineering enhanced productivity in a type III polyketide synthase, and a rare instance of improving the activity of a biosynthetic enzyme from secondary metabolism.

Type III polyketide synthases have a substantial role in the biosynthesis of various polyketides in plants and microorganisms. Comparative proteomic analysis of type III polyketide synthases showed evolutionarily and structurally related positions in a compilation of amino acid sequences from different families. Bacterial and fungal type III polyketide synthase proteins showed <50% similarity b...

Polyketides are a diverse group of natural products that form the basis of many important drugs. The engineering of the polyketide synthase (PKS) enzymes responsible for the formation of these compounds has long been considered to have great potential for producing new bioactive molecules. Recent advances in this field have contributed to the understanding of this powerful and complex enzymatic...

Virginiamycin M (VM) of Streptomyces virginiae is a hybrid polyketide-peptide antibiotic with peptide antibiotic virginiamycin S (VS) as its synergistic counterpart. VM and VS belong to the Streptogramin family, which is characterized by strong synergistic antibacterial activity, and their water-soluble derivatives are a new therapeutic option for combating vancomycin-resistant Gram-positive ba...

Combinatorial biosynthesis approaches that involve modular type I polyketide synthases (PKSs) are proven strategies for the synthesis of polyketides. In general however, such strategies are usually limited in scope and utility due to the restricted substrate specificity of polyketide biosynthetic machinery. Herein, a panel of chemo-enzymatically synthesized acyl-CoA's was used to probe the prom...

Two genes involved in aflatoxin B1 (AFB1) biosynthesis in Aspergillus parasiticus, nor-1 and ver-1, were localized to a 35-kb region on one A. parasiticus chromosome and to the genomic DNA fragment carried on a single cosmid, NorA. A physical and transcriptional map of the 35-kb genomic DNA insert in cosmid NorA was prepared to help determine whether other genes located in the nor-1-ver-1 regio...