Biosynthetic Pathways and Engineering for Bioactive Natural Products

Abstract

Natural products synthesized by polyketide synthase (PKS), non-ribosomal peptide synthetase (NRPS) and the hybrid PKS-NRPS have been valuable sources for bioactive compounds due to their structural diversity and wide variety of biological activities. Progresses in the biosynthetic study of natural products in recent years reinvigorate the hope of discovering new compounds for clinical use. This review focuses on the elucidation of biosynthetic pathways of PKS and NRPS, the more "abnormal" biosynthetic reactions, the manipulation of gene cluster to increase product yields, as well as the catalytic applications of the enzymes originated from secondary metabolism. Genome mining or key regulatory gene activation to obtain "silent" gene cluster and the progresses on using sequencing data to predict the generation of natural products are also summarized.

Metabolic Profile, Biotransformation, Docking Studies and Molecular Dynamics Simulations of Bioactive Compounds Secreted by CG3 Strain

“…These compounds can be obtained in two ways: (i) The first way is the biosynthetic pathway: in this case, Actinobacteria use different enzymes, such as polyketide synthase (PKSI, PKII and PKSIII) [6], non-ribosomal peptide synthase (NRPS) [7] and the hybrid PKS-NRPS [8], for the biosynthesis of secondary metabolites. PKS enzymes use an extender unit, which is usually an acyl-COA such as malonyl-CoA, methylmalonyl-CoA, ethylmaloyl-CoA or methoxymalonyl-COA, for the biosynthesis of polyketide molecules [9]. However, NRPS enzymes use different monomers of proteinogenic and nonproteinogenic amino acids for the biosynthesis of non-ribosomal peptides [10].…”

A novel docking domain interface model predicting recombination between homoeologous modular biosynthetic gene clusters

“…Modular biosynthetic clusters, e.g., polyketide synthases (PKS) or non-ribosomal peptide synthetases (NRPS), are particularly interesting for evolutionary studies as they function according to an ''assembly line'' principle in which each module is usually responsible for a single extension step during the synthesis of the product and the growing chain is passed from module to module until complete. The chemistry is understood in considerable details [13,15,19,31,36] and is summarized briefly below.…”

A Multidisciplinary Approach to Unraveling the Natural Product Biosynthetic Potential of a Streptomyces Strain Collection Isolated from Leaf-Cutting Ants

“…These strains belong to clade C1, which, as mentioned before, only contains one of the model strains used in this study (S. clavuligerus) (Figure 1) and harbor in their genomes more singletons than the rest of the strains analyzed (15 and 18, respectively). Also, over half of these singletons belong to the NRPS, PKS or hybrid NRPS/PKS BGC classes, which are well known as sources of bioactive compounds [61,62].…”