A PhD student at DTU Department of Biotechnology and Biomedicine has developed a new method which enables faster determination of organisms’ potential to produce certain substances. The results can be used to create new and better cell factories more rapidly and can reveal pathogenicity in organisms we thought were harmless.
Secondary metabolites are chemical substances that plants and microorganisms produce or have the potential to produce which they are not directly dependent on to survive and grow. They are used, for example, for defence against insects or as antioxidants. Industry uses secondary metabolites extensively to produce many different substances such as, enzymes, insulin, medicine, pigments and sustainable biofuels. Researchers and industry are therefore always on the lookout for new secondary metabolites and new ways of exploiting those that are already known.
It is a comprehensive task, but relatively straightforward to identify what kind of substance the organism produces, but it is far more challenging to identify the genes that code for the particular substance, that is, how the organism produces it. It is even more difficult to reveal the hidden potential for producing a given substance, but a new method developed by Inge Kjaerbølling, a PhD student at DTU Bioengineering, will make this easier.
The method is used in a study recently published in the respected scientific journal PNAS. The study, conducted in close collaboration between DTU Department of Biotechnology and Biomedicine (DTU Bioengineering) and the American research beacons DoE Joint Genomic Institute (JGI) and DoE Joint Bioenergy Institute, deals with four fungi from the Aspergillus family.
"For example, our new method revealed pathogens in a mould that we previously thought was harmless. It turned out that the mould fungus A. novofumigatus is potentially just as dangerous as A. fumigatus, which causes Invasive Aspergilliosis, a fungal infection entering the body through the respiratory tract, which is lethal in 40 out of 100 cases"
Inge Kjærbølling, PhD Student at DTU Bioengineering
Aspergillus is a family of mould fungi occurring in microbial populations all over the world, and already used on a large scale in industrial production. In the study, the researchers show that the new methods can identify the gene clusters faster, i.e. the collections of genes responsible for producing a given substance. This paves the way for finding out how to produce more of the substance so it can be used in cell factories.
The researchers produced whole-genome sequencing for each of the four mould fungi, and they compared those results to known species that had been sequenced previously. Comparative genetics—in which certain portions of the genome are compared to the same parts in another organism—can be used to discover many hidden properties with the potential to become new drugs such as antimicrobial agents, cholesterol-lowering agents, etc. Inge Kjaerbølling explains how her method takes things one step further:
“We combine the results from comparative genetics with our knowledge of how secondary metabolites are produced in cells. In this way, we link known secondary metabolites with the responsible genes. Once we know the genes, it is relatively straightforward to search for them in other organisms, and this increases the likelihood of finding new drugs, new food ingredients or other valuable substances.”
The method can also be used to discover hidden properties and thus investigate whether organisms have potential pathogenicity we should be aware of.
“For example, our new method revealed pathogens in a mould that we previously thought was harmless. It turned out that the mould fungus A. novofumigatus is potentially just as dangerous as A. fumigatus, which causes Invasive Aspergilliosis, a fungal infection entering the body through the respiratory tract, which is lethal in 40 out of 100 cases,”
Inge Kjaerbølling explains.
“This project is ongoing, and now we must continue to work on this large amount of material with even more whole-genomic sequencing. It will be interesting to see what we can learn from this and what interesting new gene clusters we can identify using Inge Kjaerbølling’s new method.”
The study is based on the extensive fungal collection of more than 30,000 species kept in freezers in the basement at DTU, and is the first result of a major project in which researchers sequence the genomes of 300 Aspergillus species. Senior author and Professor Mikael Rørdam Andersen says:
“This project is ongoing, and now we must continue to work on this large amount of material with even more whole-genomic sequencing. It will be interesting to see what we can learn from this and what interesting new gene clusters we can identify using Inge Kjaerbølling’s new method.”
Read the article in PNAS Linking secondary metabolites to gene clusters through genome sequencing of six diverse Aspergillus species
Listen to senior author, Professor Mikael R. Andersen, talking about the project here.
The study was supported by Villum Fonden and the Novo Nordisk Foundation.