Unpacking a New Bacterial Mini-Factory
Many bacteria contain microcompartments that function like mini-factories, efficiently processing compounds for diverse purposes. For example, they sequester toxic intermediates in organisms like the notorious Salmonella and Escherichia; or in cyanobacteria, they enhance the efficiency of photosynthesis.
The MSU-DOE Plant Research Lab’s Kerfeld lab under the direction of Cheryl Kerfeld, Hannah Distinguished Professor of Structural Bioengineering in the Department of Biochemistry and Molecular Biology, is at the forefront of understanding different kinds of these bacterial microcompartments – how they work and are built – with the goal of bioengineering them someday to produce sustainable energy sources and other “green” or medical products, without using fossil fuels.
And in a recent publication in Scientific Reports, Jan Zarzycki, a former post-doc in the Kerfeld lab, describes a new microcompartment widely spread among different kinds of bacteria, increasing our understanding of the enzymes packed within it.
Although many bacterial microcompartments share a common way of processing compounds into useful products, they differ in what compounds they employ as raw materials.
“These compartments’ functions are defined by what enzymes they package,” says Jan, currently a post-doc with Dr. Tobias Erb at the Max Planck Institute for Terrestrial Microbiology. “Specifically, the enzyme that catalyzes the very first step of the reaction sequence determines the overall function.”
The defining enzyme in Jan’s newly described microcompartment is a so-called glycyl radical enzyme (GRE).
“GREs that are not associated with microcompartments have been widely studied. However, now, in the era of genome sequencing, tons of GRE encoding genes are popping up in databases, many accompanied by bacterial microcompartment genes. These GREs appear to have novel functions inside the mini-factories, and some functions have been recently described.”
Jan adds that although these functions can sometimes be predicted with bioinformatics methods, the challenge is to demonstrate them in the lab.
“Unfortunately, GREs are hard to directly examine, because they are destroyed after the slightest contact with oxygen. It took us a lot of effort to work with a GRE under strictly oxygen-free conditions, but we were able to determine and prove its function, and thus the function of the microcompartment it is involved with.”
From biology to engineering
Synthetic biologists are very interested in the versatility of the GREs and their microcompartments, as they could become a platform for designing molecular pathways that sustainably produce “green” chemicals, medicines, renewable materials like rubber, even renewable energy.
“In the big picture, in order to transform biology to become a real engineering science, we first need to understand how nature, and in this case, microcompartments work. This knowledge would enable us to potentially reassemble those mini-factories to perform these new functions in both bacteria and plants.”
“Biologists can already engineer single enzymes that work as well, if not better, than natural ones. But building complex systems with multiple enzymes is still a great challenge, because we often don’t understand the natural systems well enough.”