Within these microbes, the drugs are developed by incredibly small natural machines, or mega-enzymes, also known as nonribosomal peptide synthetases (NRPSs). A study conducted by a team at McGill University has reportedly got a better understanding of the systems of NRPSs and the structure according to which they function. This allegedly enhanced understanding of NRPSs, with researchers saying that it could allow bacteria and fungi to be handled for the production of new compounds. It could also lead to the creation of new antibiotics, immunosuppressants, and other types of drugs.
“NRPSs are really fantastic enzymes that take small molecules like amino acids or other similar-sized building blocks and assemble them into natural, biologically active, potent compounds, many of which are drugs,” said Martin Schmeing, Associate Professor in the Department of Biochemistry at McGill University, and co-author of the paper published in the journal Nature Chemical Biology. “An NRPS works like a factory assembly line that consists of a series of robotic workstations. Each station has multi-step workflows and moving parts that allow it to add one building block substrate to the growing drug, elongating and modifying it, and then passing it off to the next little workstation, all on the same huge enzyme.”
Working With Ultra-Intensive Light Rays
In their article published in May 2020 in the journal Nature Chemical Biology, the scientists reported seeing an NRPS mechanical system by utilizing the CMCF beamline form the Canadian Light Source (CLS). The CLS is a national laboratory that manufactures the ultra-intense beams of X-rays needed to visualize proteins, even mega-enzymes that are too tiny to be observed with any light microscope.
“Scientists have long been excited about the potential of bioengineering NRPSs by identifying the order of building blocks and reorganizing the workstations in the enzyme to create new drugs, but the effort has rarely been successful,” explained Schmeing. “This is the first time anyone has seen how these enzymes transform keto acids into a building block that can be put into a peptide drug. This helps us understand how the NRPSs can use so very many building blocks to make the many different compounds and therapeutics.”