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The Humanicsxian: September 09: Issue 04
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|| Modifying Enzymes to Re-engineer Plant Cell Wall: Many Fields May Benefit  ||


|| Friday: September 22: 2023 || ά.  A newly discovered way of optimising plant enzymes through bio-engineering has increased knowledge of how plant material can be converted into bio-fuels, bio-chemicals and other high-value products. The University of Adelaide-led study presents innovative ideas for how the walls of plant cells can be assembled, structured and remodelled by controlling specific enzymes’ catalytic function.

Fundamental plant cell properties, such as, structure, integrity, cytoskeletal organisation and stability, are now viewed differently, suggesting new alternatives. Studying the catalytic function of specific enzymes, a process, termed, 'xyloglucan xyloglucosyl transferases', allowed the researchers to better understand how they link diverse polysaccharides to form structural components of plant cell walls.

“This work contributes to the essential knowledge of how xyloglucan xyloglucosyl transferases can be understood and their fundamental properties controlled; for example, to improve their catalytic rates and stability.” Said the Project Leader Professor Maria Hrmova. For plant material to be used in the production of bio-fuels, plant cell walls need to be deconstructed and the resultant materials chemically processed.

The properties of the cell walls can be altered to be less rigid, therefore, making bio-fuel production more efficient and cost-effective. The finding, also, has applications for the pharmaceutical industry, where enzymes are sought as environmentally friendly and cost-effective options in bio-remediation and other applications.

Bio-remediation is the removal of contaminants, pollutants and toxins from the environment through the use of living organisms. “Although, the definition of the catalytic function of xyloglucan xyloglucosyl transferases has significantly progressed during the past 15 years, there are limitations, and still a lack of information, in how this knowledge can be organically implemented in the functionality of plant cell walls.” Professor Maria Hrmova said.

This teamwork builds upon 60 years of xyloglucan chemical and biochemical research of this and other research groups. The research team used sensitive high-performance liquid chromatography with fluorescent reagents to monitor complex bio-chemical reactions of polysaccharides in an efficient way.

“We, also, applied three-D molecular modelling and molecular dynamics simulations to gain insights into the mode of action of these enzymes on fast time scales.” Professor Hrmova said.

“Our findings are supported by plant and cellular biology approaches we used to offer novel ideas on the function of these enzymes in vivo.”

The Study was published in the Plant Journal and was conducted with an international, multi-disciplinary team of researchers from the Institute of Chemistry of the Slovak Academy of Sciences and the Huaiyin Normal University in China. It, also, received funding support from the VEGA Scientific Grant Agency and the Australian Research Council.

|| ΕΛ || Caption: A three-D image of nasturtium xyloglucan xyloglucosyl transferase with bound substrate reactants: || ΕΛ ||  

|| Readmore at || || 230923 ||



|| Potent New Compound Cyanotriazole Discovery Has Breakthrough Potential For Sleeping Sickness and Chagas Disease: Cyanotriazoles Selectively Bind to Parasite Enzyme Topoisomerase II and Create Lethal Condition to the Parasites ||



|| Thursday: August 31: 2023 || ά. Scientists have discovered a new class of compound, that is, potentially, active against trypanosome parasites, that cause human African Trypanosomiasis or sleeping sickness and Chagas Disease. The ground-breaking findings, published in the journal Science.  The potent compounds discovered for the two separate types of Trypanosomiases, showing potential for development as new medicines for these diseases.

The Study demonstrated that the compounds were able to cure a mouse model of sleeping sickness with just a single dose and a short course of daily doses across five days cured Chagas Disease in the same models. African Trypanosomiasis or sleeping sickness, is a major killer disease, which puts around 70 million people at risk in Sub-saharan African countries and is invariably fatal, if, untreated or inadequately treated. Meanwhile, around seven million people are currently infected by Chagas Disease, which can cause irreversible damage to the heart and digestive tract.

There are currently no drugs available that, effectively, cure Chagas Disease; while for sleeping sickness, there have been some steps forward toward new therapies in recent years. The researchers, also, show in the Study exactly how the compounds, called, Cyanotriazoles, or CTs for short, kill parasites without adversely affecting host cells. These compounds selectively bind to a parasite enzyme, called, topoisomerase II. that is essential for the replication and maintenance of DNA, which carries the genetic blueprint vital for life. By binding to and inhibiting this enzyme, the compounds introduce breaks into the DNA, that are lethal to the parasites.

The Glasgow group, led by Professor Mike Barrett from the Wellcome Centre for Integrative Parasitology in the University’s School of Infection and Immunity, made inroads into finding that mechanism of action using a technique, known as, metabolomics, through the Glasgow Polyomics facility, which showed how DNA was being degraded in the cells.  Parasites resistant to the drugs had changed their topoisomerase protein structure such that they no longer bound the drug.

The Novartis team, led by Srini Rao, worked out the three-dimensional structure of the trypanosome’s topoisomerase, showing how CTs bind to a particular part of the trypanosome’s enzyme, that is absent from the human version.

Professor Mike Barrett, of Biochemical Parasitology at the University of Glasgow, said, “Compounds with this degree of potency, working through a newly discovered mechanism, represent a major breakthrough.  If, they are proven to be safe in humans and retain the levels of activity seen in mice, they could offer the first effective therapy of Chagas Disease, which afflicts millions of people in Latin America.”

The Paper: Cyanotriazoles are selective topoisomerase II poisons that rapidly cure trypanosome infections: Published in Science :::ω:::  

|| Readmore  || ||  010923 ||


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