Field Of Natural Product Research Research Articles

Challenges and triumphs to genomics-based natural product discovery

Genome sequencing is rapidly changing the field of natural products research by providing opportunities to assess the biosynthetic potential of strains prior to chemical analysis or biological testing. Ready access to sequence data is driving the development of new bioinformatic tools and methods to identify the products of silent or cryptic pathways. While genome mining has fast become a useful approach to natural product discovery, it has also become clear that identifying pathways of interest is much easier than finding the associated products. This has led to bottlenecks in the discovery process that must be overcome for the potential of genomics-based natural product discovery to be fully realized. In this perspective, we address some of these challenges in the context of our work with the marine actinomycete genus Salinispora, which is proving to be a useful model with which to apply genome mining as an approach to natural product discovery.

Policosanols lose their lustre as cholesterol-lowering agents

Policosanols have been purported by one research group to act as effective agents for LDL-cholesterol (LDL-C) lowering in humans. However data from independent researchers have been contradicting results published by the laboratories originating these claims. The purpose of this commentary is therefore to briefly summarize the policosanol controversy and point out the potential explanations for inconsistencies in the policosanol literature, as well as to determine potential origins of the problem especially at the level of the reviewing and publishing process. Scrutiny and vigilance at all steps of the process are necessary in order to avoid such controversies in the field of natural product research.

Bioinformatic perspectives on NRPS/PKS megasynthases: Advances and challenges

The increased understanding of both fundamental principles and mechanistic variations of NRPS/PKS megasynthases along with the unprecedented availability of microbial sequences has inspired a number of in silico studies of both enzyme families. The insights that can be extracted from these analyses go far beyond a rough classification of data and have turned bioinformatics into a frontier field of natural products research. As databases are flooded with NRPS/PKS gene sequence of microbial genomes and metagenomes, increasingly reliable structural prediction methods can help to uncover hidden treasures. Already, phylogenetic analyses have revealed that NRPS/PKS pathways should not simply be regarded as enzyme complexes, specifically evolved to product a selected natural product. Rather, they represent a collection of genetic opinions, allowing biosynthetic pathways to be shuffled in a process of perpetual chemical innovations and pathways diversification in nature can give impulses for specificities, protein interactions and genetic engineering of libraries of novel peptides and polyketides. The successful translation of the knowledge obtained from bioinformatic dissection of NRPS/PKS megasynthases into new techniques for drug discovery and design remain challenges for the future.

Production platforms for the molecular pharming of alkaloid diversity

The field of natural products research has been experiencing a renaissance of interest for quite some time now, led in large part by a combination of practical realities, exciting new discoveries, and the development of some intriguing new concepts. Chemical, agricultural, food, and personal care products industries have all benefited from this arena of research. Nonetheless, the drug development pipeline has probably benefited the most from our fascination with natural products, and largely because of the structural complexity and diversity of compounds biosynthesized by natural sources as compared with those compounds arising from strictly an organic synthesis origin. The notion that natural products provide a greater opportunity for drug discovery and development than pure synthetic approaches has also been argued for some time now and is evident in the results presented by Minami et al. (1) in a recent issue of PNAS. The recent reports by Newman et al. (2, 3) also clearly document how approximately two-thirds of the drugs developed over the last 25 years have been derived from or inspired by particular natural products. Feher and Schmidt (4) provided an additional compelling argument as to why natural products have served so well for drug development. These investigators reported that the structural complexity found in drugs, as measured by the average number of 2.3 chiral centers per drug molecule, more closely resembled that found in natural products (average of 6.2 chiral centers per molecule) than the relative flat molecules (0.4 chiral centers per compound) found in libraries prepared by synthetic, combinatorial means (Fig. 1).