Metabolic model for diversity-generating biosynthesis.

A conventional metabolic pathway leads to a specific product. In stark contrast, there are diversity-generating metabolic pathways that naturally produce different chemicals, sometimes of great diversity. We demonstrate that for one such pathway, tru, each ensuing metabolic step is slower, in parallel with the increasing potential chemical divergence generated as the pathway proceeds.

Assessing the combinatorial potential of the RiPP cyanobactin tru pathway.

Ribosomally produced natural products, the RiPPs, exhibit features that are potentially useful in the creation of large chemical libraries using simple mutagenesis. RiPPs are encoded on ribosomal precursor peptides, but they are extensively posttranslationally modified, endowing them with properties that are useful in drug discovery and biotechnology. In order to determine which mutations are acceptable, strategies are required to determine sequence selectivity independently of the context of flanking amino acids.

Accessing the hidden majority of marine natural products through metagenomics.

Tiny marine animals represent an untapped reservoir for undiscovered, bioactive natural products. However, their small size and extreme chemical variability preclude traditional chemical approaches to discovering new bioactive compounds. Here, we use a metagenomic method to directly discover and rapidly access cyanobactin class natural products from these variable samples, and provide proof-of-concept for genome-based discovery and supply of marine natural products.

Progress in the delivery of therapeutic oligonucleotides: organ/cellular distribution and targeted delivery of oligonucleotides in vivo.

Oligonucleotide (ODN) therapy is a powerful tool for modulation of gene expression in vivo. With advances in ODN chemistry and progress in formulation development, ODNs are becoming widely acceptable drugs. This review summarizes the current status and future trend of the in vivo application of ODN therapeutics, especially antisense ODNs.