Prof. Neil Kelleher, MicroMGx’s Chairman of the Board, co-authored a published article in ACS Chemical Biology, 2020, again showing the efficacy of using the metabologenomics platform to identify new bioactive compounds and a new biosynthetic gene cluster. Learn more about the published article below. Congratulations Prof. Neil Kelleher!
Montaser, R; Kelleher, N L
Discovery of the Biosynthetic Machinery for Stravidins, Biotin Antimetabolites
Stravidins are peptide antibiotics produced by Streptomyces spp. Their antibacterial activity derives from an unusual amiclenomycin monomer, the warhead that inhibits biotin biosynthesis. Despite being discovered over five decades ago, stravidin biosynthesis has remained a mystery. Using our “metabologenomics” platform, we discover new stravidin analogues and identify the novel biosynthetic machinery responsible for their production. Analysis of the newly identified biosynthetic gene cluster (BGC) indicates the unusual amiclenomycin warhead is derived from chorismic acid, with initial steps similar to those involved in p-amino phenylalanine biosynthesis. However, a distinctive decarboxylation retains the nonaromatic character of a key ring and precedes a one-carbon extension to afford the warhead in its bioactive, untriggered state. Strikingly, we also identified two streptavidin genes flanking the new stravidin BGC reported here. This aligns with the known synergistic activity between the biotin-binding activity of streptavidin and the stravidins to antagonize both biotin biogenesis and bacterial growth.
Actinobacteria is a phylum of Gram-positive bacteria with high guanine and cytosine content in their DNA. Although understood primarily as soil bacteria, they might be more abundant in freshwaters. Considered to be one of the most prolific producers of natural products.
Bacteria are single celled microbes. The cell structure is simpler than that of other organisms as there is no nucleus or membrane bound organelles. Instead their control centre containing the genetic information is contained in a single loop of DNA.
A biological system is a complex network of biologically relevant entities. As biological organization spans several scales, examples of biological systems are populations of organisms, or on the organ- and tissue scale in mammals and other animals, the circulatory system, the respiratory system, the nervous system, etc.
On the micro- to the nanoscopic scale, examples of biological systems are cells, organelles, macromolecular complexes and regulatory pathways.
High-performance liquid chromatography (HPLC; formerly referred to as high-pressure liquid chromatography), is a technique in analytical chemistry used to separate, identify, and quantify each component in a mixture. It relies on pumps to pass a pressurized liquid solvent containing the sample mixture through a column filled with a solid adsorbent material.
Mass Spectrometry (MS) is an analytical chemistry technique that helps identify the amount and type of chemicals present in a sample by measuring the mass-to-charge ratio and abundance of gas-phase ions.
Metabolites are the intermediates and products of metabolism. The term metabolite is usually restricted to small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, catalytic activity of their own (usually as a cofactor to an enzyme), defense, and interactions with other organisms (e.g. pigments, odorants, and pheromones).