Construction of Powerful Antibiotics in Microbes
How a powerful antibiotic is formed in nature is not a mystery anymore, according to a recent study conducted at University of Illinois. Researchers report in the journal Nature that their work has made a breakthrough in understanding how a powerful antibiotic agent is made in nature solving a decades-old mystery.
The team focused on a class of compounds consisting of numerous antibiotic properties. The most common candidate compound among them is ‘nisin’, a natural product present in milk. Nisin can be synthesized in lab. It is used as a preservative and anti-microbial agent since 1960
Though the sequence of the nisin gene is long known and its gene product can be assembled, the modifications happen after the peptide chain formation is an unsolved problem so far. These modifications are required for its final structure and function. Special enzymes are required for this purpose. For nisin, a dehydratase enzyme is needed to give the antibiotic its final, three-dimensional shape. Nisin has several rings and these rings are essential for nisin’s antibiotic function: Two of them disrupt the construction of bacterial cell walls, while the other three punch holes in bacterial membranes. This dual action makes it much more difficult for microbes to develop antibiotic resistance. However, how the dehydratase modifies nisin is not known yet.
The recent findings suggest that amino acid glutamate is essential for nisin’s transformation. The enzyme dehydratase serves two purposes, it adds glutamate to nisin and on the other hand it eliminates glutamate. How one enzyme showed two different activities at the same time, is shown by using X-ray crystallography. It is found that the enzyme interacts with the peptide in two ways: It grasps one part of the peptide and held it fast, while a different part of the dehydratase helps to install the ring structures. This glutamate is supplied by transfer-RNAs.
This study solves a lot of questions regarding the mechanism of dehydration. A large number of natural products with therapeutic potential are formed in similar fashion. This study opens up new avenues of research into thousands of similar molecules, many of which have the potential to be used therapeutically.
More information: “Structure and mechanism of the tRNA-dependent lantibiotic dehydratase NisB,” Nature, 2014. DOI: 10.1038/nature13888
Latest posts by Arunima Maiti (see all)
- Sea oysters: another victim of plastic pollution - February 20, 2016
- Spermbots: Remote-controlled sperm, for assured fertilization - January 19, 2016
- Green Tea: Not a Super-food? - December 11, 2015
- Yellow-bellied Water Snake Mom Gives ‘Virgin Birth’ - September 26, 2015
- Production of Sperm in a Dish in 72 days - September 25, 2015