Natural Products: Nature’s Hidden Helpers
Discover the role of natural products in medicine and agriculture.
Jonathan J. Ford, Javier Santos-Aberturas, Edward S. Hems, Joseph W. Sallmen, Lena A. K. Bögeholz, Guy Polturak, Anne Osbourn, Joseph A. Wright, Marina V. Rodnina, Danny Vereecke, Isolde M. Francis, Andrew W. Truman
― 5 min read
Table of Contents
- A Closer Look at Actinonin and Matlystatin
- The Role of Mutases in Discovery
- Meet Rhodococcus fascians
- The Discovery of Lydiamycin A
- The Mystery of the Structure
- Lydiamycin's Action Against Peptide Deformylase
- Defending Against the Competition
- The Role of Antimicrobial Compounds
- Finding New Allies in Nature
- Conclusion: A World of Possibilities
- Original Source
Natural products (NPs) are like the cool gadgets of the living world. They help various organisms communicate, find nutrients, and even throw a few roadblocks in the way of their competitors. You can find NPs doing an impressive array of jobs in medicine and farming, like fighting infections and treating diseases. In fact, most of the antibiotics we have today come from these natural wonders.
A Closer Look at Actinonin and Matlystatin
Two notable players in the natural product arena are actinonin and matlystatin, both of which come from a group of bacteria called actinobacteria. These two share a similar chemical component known as HPS, which is quite the multitasker. It grabs onto metal ions, making it an efficient partner for the metalloprotein enzymes. Actinonin is particularly impressive, showing strong activity against various diseases in mice, such as cancer and malaria. It even targets certain types of bacteria, which is always a plus when you're in the business of fighting germs.
The Role of Mutases in Discovery
In the quest to find more natural products like actinonin and matlystatin, scientists have turned to a special group of enzymes called mutases. By looking at the genes related to these mutases and their surroundings, researchers can unearth new biosynthetic gene clusters (BGCs), which are essentially the blueprints for making these beneficial natural substances. This method has led to some exciting findings, including new candidates for metalloprotease inhibitors, compounds that can block certain proteins involved in disease.
Meet Rhodococcus fascians
One of the characters in our story is Rhodococcus fascians, a mischievous plant pathogen known for causing leafy gall disease in various plants. This little troublemaker can wreak havoc on the ornamental plant industry. R. fascians possesses a special plasmid that helps it cause disease and make various natural products that interfere with plant growth. This makes it a case study for understanding how these tiny molecules interact with the larger world around them.
The Discovery of Lydiamycin A
Researchers stumbled upon a particular BGC in the R. fascians DNA that seemed to produce something called lydiamycin A. This compound had been previously isolated as an antibiotic from another type of bacteria, but its full story was still a bit hazy. After some investigation, it became clear that lydiamycin A, much like actinonin, also features an HPS-like moiety. This connection was not obvious at first, and it took several rounds of analysis to confirm the relationship.
The Mystery of the Structure
When comparing lydiamycin A to actinonin and matlystatin, some structural differences emerged. At first glance, it seemed there was a mismatch in how certain parts of these molecules connected. However, through more detailed examinations using various techniques, scientists began to sort out the confusion and proposed a new structure for lydiamycin A, revealing similarities to its well-known cousins.
Lydiamycin's Action Against Peptide Deformylase
Now that researchers had a clearer picture of lydiamycin A, they turned their attention to how it works. They discovered that it inhibits an enzyme called peptide deformylase (PDF), which plays a critical role in the growth of certain bacteria. In fact, actinonin is known for being a strong PDF inhibitor, and researchers suspected that lydiamycin A could be in the same league.
Defending Against the Competition
Lydiamycin A isn’t just a lone wolf; it plays a role in helping R. fascians fend off its competitors. In the battle for survival on plants, producing lydiamycin A gives this bacterium an edge against others that might want to share the same turf. Through experiments, scientists found that when R. fascians produces lydiamycin, it can better compete against other bacteria, making survival less of a struggle.
The Role of Antimicrobial Compounds
Antimicrobial compounds like lydiamycin A are more than just fancy science words; they are crucial for many living organisms. Not only do they protect the producers, but they can also influence the ecology of their environments. By producing such compounds, R. fascians can shape its surroundings and possibly impact plant health as well. The interconnected world of microbes and plants is much more complex than we often realize.
Finding New Allies in Nature
The quest for new natural products doesn't end here. With the knowledge gained from studying R. fascians and its ability to produce lydiamycin A, scientists now have a road map to discover other potential natural products. By looking into related bacteria and their BGCs, it’s possible to find even more hidden treasures that might hold the key to new treatments for diseases or innovative agricultural solutions.
Conclusion: A World of Possibilities
In summary, natural products like actinonin, matlystatin, and lydiamycin A showcase the incredible potential of nature's chemistry. By studying these compounds and their biosynthetic pathways, we're not just uncovering their secrets; we're opening the door to new medicines and eco-friendly solutions for farming. So the next time someone mentions the power of nature, just nod knowingly-there's a lot happening behind the scenes that we are only just beginning to understand.
Title: Discovery of lydiamycin A biosynthetic gene cluster in the plant pathogen Rhodococcus fascians guides structural revision and identification of molecular target
Abstract: The natural products actinonin and matlystatin feature an N-hydroxy-2-pentyl-succinamyl (HPS) chemophore that facilitates metal chelation and confers their metalloproteinase inhibitory activity. Actinonin is the most potent natural inhibitor of peptide deformylase (PDF) and exerts antimicrobial and herbicidal bioactivity by disrupting protein synthesis. Here, we used a genomics-led approach to identify candidate biosynthetic gene clusters (BGCs) hypothesised to produce novel HPS-containing natural products. We show that one of these BGCs is on the pathogenicity megaplasmid of the plant pathogen Rhodococcus fascians and produces lydiamycin A, a macrocyclic pentapeptide. The presence of genes predicted to make a HPS-like chemophore informed the structural recharacterisation of lydiamycin via NMR and crystallography to show it features a rare 2-pentyl-succinyl chemophore. We demonstrate that lydiamycin A inhibits bacterial PDF in vitro and show that a cluster-situated PDF gene confers resistance to lydiamycin A, representing a novel self-immunity mechanism associated with the production of a PDF inhibitor. In planta competition assays showed that lydiamycin enhances the fitness of R. fascians during plant colonisation. This study highlights how a BGC can inform the structure, biochemical target and ecological function of a natural product.
Authors: Jonathan J. Ford, Javier Santos-Aberturas, Edward S. Hems, Joseph W. Sallmen, Lena A. K. Bögeholz, Guy Polturak, Anne Osbourn, Joseph A. Wright, Marina V. Rodnina, Danny Vereecke, Isolde M. Francis, Andrew W. Truman
Last Update: 2024-11-13 00:00:00
Language: English
Source URL: https://www.biorxiv.org/content/10.1101/2024.11.13.623425
Source PDF: https://www.biorxiv.org/content/10.1101/2024.11.13.623425.full.pdf
Licence: https://creativecommons.org/licenses/by-nc/4.0/
Changes: This summary was created with assistance from AI and may have inaccuracies. For accurate information, please refer to the original source documents linked here.
Thank you to biorxiv for use of its open access interoperability.