A team of researchers from the Eichman lab and associated with the Evolutionary Studies Initiative led a project that was recently published. The work was co-authored by graduate student Noah Bradley and undergraduate studentKatie Wahl.
The group was interested in natural products. These chemicals are produced by the organisms for a specific purpose, but can be valuable if used as antibiotics, anticancer agents, or other therapeutic agents. The importance of finding new weapons against resistant-diseases is increasing as new drug-resistant strains of diseases evolve.
In this study, the researchers used a technique known as genome mining, which Bradley describes as a useful tool in identifying gene clusters and natural products they produce. The mechanism used to produce a natural product has historically been targeted by genome mining. The team's approach is to target processes that givebacteria self-resistance towards a specific type of compound. They were interested in mining for natural products that can form a chemical bond to DNA.
The group paid special attention to two genes.
One, AlkZ, is found in Streptomyces sahachiroi while the other, YcaQ, is found in Escherichia coli. Genotoxins can cause DNA damage, and these enzymes can remove it. The functions and environments of AlkZ and YcaQ are very different.
AlkZ-like (AZL) enzymes tend to localize within biosynthetic gene clusters and according to Bradley, they seem to be tailored for self-resistance to specific natural products.
According to Wahl, the YQL proteins might be general caretakers to remove a variety of DNA damage, since it has not been found in clusters.
The authors are excited about what the results mean.
In the short term, we hope that the approximately 70 uncharacterized gene clusters we identified in our study can be screened for the targeted discovery of novel or useful genotoxic natural products.
In the long term, we are hopeful that our self-resistance-guided genome mining framework will be applied in the scientific community for the targeted discovery of natural products of therapeutic benefit. We envision the discovery of new repair mechanisms through this approach.
The project was born out of creativity because of the COVID-19 Pandemic. The work ethic and positive attitudes of Bradley and Wahl were reflected by Eichman.
I enjoyed watching Noah andKatie execute a project that they designed specifically to be done at home during the lab shut-down period. He said that the study has paved the way for an entirely new avenue of research for the lab.
This work was an example of interdisciplinary research going on.
The project began at the beginning of the epidemic and evolved into a fruitful collaboration with a graduate student in the lab.
The Mass Spectrometry Research Center (MSRC) provided assistance with critical experiments in this project.
More information: Noah P. Bradley et al, Resistance-Guided Mining of Bacterial Genotoxins Defines a Family of DNA Glycosylases, mBio (2022). DOI: 10.1128/mbio.03297-21 Journal information: mBio Citation: Researchers use new method to target potentially undiscovered beneficial therapeutic chemicals (2022, April 5) retrieved 6 April 2022 from https://phys.org/news/2022-04-method-potentially-undiscovered-beneficial-therapeutic.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.
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