Researchers at Princeton Chemistry have discovered a biosynthetic pathway that incorporates selenium into small microbial molecules, marking the first time such atoms have been discovered in natural products, and opening new avenues in selenium biology.
The research also strongly suggests that selenium, an essential element in all kingdoms of life, may have a more important biological role in bacteria than scientists originally assumed.
Lab paper, “Biosynthesis of Selenium-Containing Small Molecules in Diverse Microorganisms,” by Chase Queiroz, fourth-year graduate student in the laboratory; Postdoctoral researchers Jonathan Huang and Nicole Hauser; And Mohamed Sayed Siamdost, Professor in the Department of Chemistry.
“This has been a bit of a closed field,” Keyrouz said. “No one has found a new route to selenium metabolism in 20 years.” “The biosynthesis of selenium proteins and selenium acids was demonstrated in the ’80s and ’90s. Since then, people have kind of assumed that these are the only things microbes do with selenium. We simply wondered if they could incorporate selenium into other small molecules? It turns out they do. “.
“Our work shows that nature has already developed pathways to incorporate this element into small molecules, sugars and secondary metabolites,” said Syamdost. “Selenium has wonderful properties that are unlike any other element found in biomolecules. Incorporating selenium into selenone, for example, makes it an even better antioxidant.” Much of the sulfur version of the molecule, but while sulfur is ubiquitous in biomolecules, the occurrence of selenium is very rare and was thought to be restricted to biopolymers.
“Nature has developed specific mechanisms for incorporating either sulfur or selenium into natural products, thus taking advantage of the unique properties of both elements through their respective pathways.”
I’m looking for selenium
The lab began their research on the assumption that selenium atoms should be found in natural products due to their ubiquitous use elsewhere. What would such a signature look like in the microbial genome, they asked?
“How do you actually see where a new drug or natural product or selenium metabolite is, how do you find it?” Kerose said. “We usually look for synthetic gene clusters – the sets of genes on the chromosome that code for the biosynthesis of such molecules. So, if we have a pathway to make a compound containing selenium, it has to be encoded by genes.”
They applied a genome mining strategy to search for genes next to selD, which encode the first step in all known selenium processes within the cell.
And fairly quickly, they found a single gene in common with selD – called senB – that caught their attention, especially because it had not previously been involved in selenium metabolism.
Further examination revealed a third, localized gene, called SenA. Queiroz hypothesized that these three genes may be involved in a new selenium biosynthesis pathway.
“First, we determined what a set of biosynthetic genes that includes the element selenium would look like,” Syed Sayamdost said. We then used bioinformatics to search for such genes and identified what we now call a ‘Sen array’ in diverse microbial genomes. “
They were able to express each of these novel genes in Escherichia coli, thus assembling the entire pathway in a test tube. This revealed the production of two small selenium-containing molecules – selenogar and a molecule called selenoin. It also revealed two enzymes that form carbon-selenium bonds, the first such enzymes to act on small biological molecules.
“Microbes put selenium into these compounds for a reason, so there must be some interesting bioactivity associated with them,” Queiroz said. “We don’t know what this is yet, but it’s very exciting. As biochemists, discoveries like this are what we wake up to every day.”