Bacteria have been a great source of active ingredients for the manufacture of many drugs, particularly antibiotics. Every living organism – animals, plants, fungi, and bacteria – are made up of vast chemical compounds that enable their interaction with, and survival in their environment; but that present in bacteria, among others, has been found to contain active ingredients that are useful in medicine, and this has paved the way for the manufacture of many drugs – antibiotics especially – from these organisms.
However, unraveling the mysteries behind the benefits of these microorganisms is quite difficult. One reason is that it is not easy to culture many types of bacteria in the laboratory. But the use of bioinformatics and modern DNA sequencing methods has made the discovery of new active ingredients from these organisms easier. And by employing this approach, the research team at ETH Zurich, led by Jorn Piel, have been able to discover new ways to synthesize peptides (small molecules of proteins) natural products which are relatively abundant in bacteria.
The researchers analyzed the genome of several bacteria. They looked for genes that code for peptides, alongside those that code for the enzymes that act on these peptides (the action of these enzymes on the peptides is what gives rise to complex natural products in the bacteria). They were able to find these genes easily using search algorithms since each one displayed a distinct pattern.
The analyses showed that the enzymes were the determiners of the type of natural products to be produced by the bacteria. So, they separated the bacteria into several groups, based on the kind of enzyme present. They were unable to identify the function of the enzymes in one of the largest groups. Therefore, to confirm the computer predictions for three of the potential ingredients from this group, they conducted lab tests where they put the relevant genes into their already cultured laboratory bacteria, to investigate the substances they produce: a ring-shaped peptide molecule with a fatty acid appendage (a lipopeptide).
The process involved in the manufacture of some already-produced antibiotics made from lipopeptides, like daptomycin, is a complex one. This is because the bacterium that produces the antibiotic also creates several kinds of natural products, of which only one is purified via an extremely difficult process before it can be used as a drug. However, this study has uncovered an easier way to generate a new class of lipopeptides to aid the easier manufacturing process of more antibiotics like daptomycin.
The researchers were able to improve on the coding sequence of the genes that control the enzymes via mutation, enabling them to create improved active ingredients. To be sure that this newly discovered active ingredient is safe to be used as a drug for human intake, the researchers are currently looking into its biological function.
The findings from this study have uncovered the discovery of new easier ways to manufacture more drugs from lipopeptides, to aid better control of bacterial infections in people suffering from them.
In addition, this study has unlocked the active ingredients for the production of novel antibiotics, making it easier for pharmaceutical companies to keep up in the race against antimicrobial resistance.
Bacteria, among other organisms, are of utmost importance in the manufacture of antibiotics, which are useful in treating bacterial infections in humans. And findings from this study have opened the door to easier production of new drugs from these microorganisms.