Researchers are using the new method to detect undetectable chemical reactions

Hoʻohana ka poʻe noiʻi ʻo Vanderbilt i ke ala hou e hoʻopaʻa i nā kemika therapeutic pono ʻole i ʻike ʻia - Evolution @ Vanderbilt

Phylogenetic association of YQL / AZL proteins in Streptomyces. (A) Azinomycin B binds with different strands of DNA to form an ICL, which is cleaved by AlkZ. (B) Formation of an ICL nitrogen complex derived from mechlorethamine and released by E. coli YcaQ. (C) Phylogenetic properties of YcaQ-like (YQL, blue) and AlkZ-like (AZL, red / orange; AZL2, gray) Streptomyces proteins (n ​​= 897). Red and orange AZL separate the catalytic bases HΦQ and QΦQ. E. coli YcaQ and S. sahachiroi AlkZ protein were identified. (D) Register for catalytic factors in YQL, AZL, and AZL2 proteins. Catalytic residues are marked with asterisks. The colors match the side chain chemistry. (E) Copy the frequency number in each Streptomyces genome as a percentage of the number of species analyzed (n = 436 species, 897 sequences). The one-way ANOVA (P) values ​​of the variance score were 0.0078 (YQL-AZL), 0.0033 (AZL-AZL2), and 0.3305 (YQL-AZL2), the latter was not significant. (F) YQL / AZL frequency frequency. The red and blue strings show the characteristics of the two families; The red bar shows the features that YQL or AZL has. aie: mBio (2022). DOI: 10.1128 / heihei.03297-21

A team of researchers from the Eichman lab in collaboration with the Evolutionary Studies Initiative led a project that is currently published. mBio. Graduates Noah Bradley and Katie Wahl (BA21, BCB) were early authors in the field studying the chemical compounds formed by bacteria.

Specifically, the company prefers a combination of chemicals that are recognized as natural products. These chemicals are released by the body for a specific reason, but are of great value because they can be used as antibiotics, anticancer agents, or other medications. As anti -drug diseases continue to grow, so does the need for new weapons to fight disease.

In this study, the researchers relied on a technology called genome mining, which Bradley described as useful in identifying gene groups and the natural products they produce. Historically, genome mining has been used to make a natural product. However, some machines can produce similar natural products; therefore, the proximity of the group in place of the processes gives the bacterium while defending itself into a specific compound type. Specifically, they want to dig for gene groups to create naturally occurring genotoxic products – things that can form a chemical bond to DNA.

The team focused on two bacterial DNA repair enzymes called DNA glycosylases.

One, AlkZ, is found in Streptomyces sahachiroi and the other, YcaQ, is found in Escherichia coli. These enzymes – and related ones – can break down DNA damage caused by genotoxins. However, the genomic environments and functions of AlkZ and YcaQ are very different.

AlkZ -like enzymes (AZL) can search in biosynthetic gene groups and according to Bradley, “AZL proteins have been shown to protect themselves in natural products.”

However, enzymes such as YcaQ (YQL) were not found in the groups and according to Wahl, “YQL proteins may be the most common carriers to remove DNA damage.”

The early writers were happy with the nature of the consequences of moving forward.

“In the short term, we hope to be able to look at about 70 uncharacterized gene groups identified in our research for the availability of naturally occurring genotoxic products,” Bradley said.

“In the long run, we hope that our self-directed genome mining framework will be used in the scientific community to obtain natural products of therapeutic benefit. We also believe in achieving that.” of new DNA editing machines in this way., ”Wahl said.

This project was based on the COVID-19 disease that required researchers from the lab. Eichman reflected on the hard work and good qualities of Bradley and Wahl.

“I’m excited to see Noah and Katie implement a project that is planned to be done at home when the lab closes. It’s a whole new way of research for the lab,” he said. he said.

This work is a good example of the interdisciplinary research taking place at Vanderbilt.

According to Bradley, “since the onset of the disease, this project has developed into a good partnership with graduate student Jacob Steenwyk of the Rokas lab where they helped with phylogenetics and genome analysis. mining. “

Bradley continued, “The Mass Spectrometry Research Center (MSRC) at Vanderbilt has also provided assistance with critical experiments on this project.”

New drug candidates are found in the bacteria

More information:
Noah P. Bradley et al, The Mining-Guided Mining of Bacterial Genotoxins to Describe a Family of DNA Glycosylases, mBio (2022). DOI: 10.1128 / heihei.03297-21

Journal information:

Presented by Vanderbilt University

Directions: Researchers use new method to record undetected adverse medical chemicals (2022, April 5) Retrieved 5 April 2022 from method-potentially-undiscovered-beneficial-therapeutic.html

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