Urban park soil microbiomes are a rich reservoir of natural product biosynthetic diversity.

Numerous therapeutically relevant small molecules have been identified from the screening of natural products (NPs) produced by environmental bacteria. These discovery efforts have principally focused on culturing bacteria from natural environments rich in biodiversity. We sought to assess the biosynthetic capacity of urban soil environments using a phylogenetic analysis of conserved NP biosynthetic genes amplified directly from DNA isolated from New York City park soils.

Culture-independent discovery of natural products from soil metagenomes.

Bacterial natural products have proven to be invaluable starting points in the development of many currently used therapeutic agents. Unfortunately, traditional culture-based methods for natural product discovery have been deemphasized by pharmaceutical companies due in large part to high rediscovery rates. Culture-independent, or "metagenomic," methods, which rely on the heterologous expression of DNA extracted directly from environmental samples (eDNA), have the potential to provide access to metabolites encoded by a large fraction of the earth's microbial biosynthetic diversity.

Mechanistic Investigation of cPMP Synthase in Molybdenum Cofactor Biosynthesis Using an Uncleavable Substrate Analogue.

Molybdenum cofactor (Moco) is essential for all kingdoms of life, plays central roles in various biological processes, and must be biosynthesized de novo. During its biosynthesis, the characteristic pyranopterin ring is constructed by a complex rearrangement of guanosine 5'-triphosphate (GTP) into cyclic pyranopterin monophosphate (cPMP) through the action of two enzymes, MoaA and MoaC. Recent studies revealed that MoaC catalyzes the majority of the transformation and produces cPMP from a unique cyclic nucleotide, 3',8-cyclo-7,8-dihydro-GTP (3',8-cH2GTP).