Shining the light on plant metabolites – Fellows’ seminar by Ntakadzeni Edwin Madala

8 December 2020

Humans have known for centuries about the nutritional and healing properties of plants but how exactly do these work and what effects are current environmental and climate changes having on plants and their interactions with humans? These are some of the questions STIAS Iso Lomso fellow Ntakadzeni Edwin Madala of the Department of Biochemistry at the University of Venda is putting under the spotlight.

STIAS Iso Lomso Fellow Ntakadzeni Edwin Madala presented his seminar on 3 December 2020

“Climate change is resulting in emerging geometrical isomers of which the full biological consequences are still unknown,” said Madala. “But we believe they hold the potential for improved drug design and the development of enriched food supplements.”

“Plants don’t rely on us for their survival, we rely on them,” he explained. “Plants produce a huge variety of phytochemicals – over 100 000 have been identified. They produce these chemicals to survive in the environment. Plants only have innate immunity, they lack adaptive immunity. They therefore rely on these chemicals as a defence mechanism to keep pathogens away. If a pathogen attacks a leaf – that leaf ‘commits suicide’ so that the pathogen doesn’t spread to the rest of the plant.”

These chemicals can also be used to kill pathogens in humans and have been shown to have both pharmacological and nutritional properties. They have been used in treatments for conditions ranging from infectious diseases such as HIV and Malaria to cancers, arthritis and pain relief.

Madala explained that the myriad of compounds plants produce have varying physical and chemical properties owing to their structural diversity. A combination of all metabolites in an organism is referred to as a metabolome and advanced analytical instrumentation such as liquid chromatography mass spectrometry (LC-MS) is used to decipher the underlying biochemical processes leading to the production of these compounds.

“Factors such as genetics and physiological status (stressors) are known to contribute towards production of metabolites in plants,” he said. “Most of these compounds operate synergistically and, as such, plants producing more of desired metabolites are known to have heightened nutraceutical qualities.”

“This is what plants have always done but, recently, excessive sunlight exposure due to ozone depletion associated with global warming and climatic change has been shown to affect the metabolite composition of several plants.”

“Due to climate change, plants are exposed to more sunlight than before – they can’t run away from it,” he added. “The sunlight causes these compounds to isomerize causing different geometrical structures.”

The structural configuration of plant metabolites is directly correlated to their biological activity. Geometrical isomers have subtle structural differences caused by stereochemistry or the chemical-bond orientation.

“Plants are creating additional metabolites of which we don’t know the consequences. We need to know if the isomers induced by enhanced sunlight exposure are good or bad,” he said.

Madala explained that for a long time, the presence of these light-induced geometrical isomers has been ignored but the use of mass spectrometry is showing that due to the ever-changing climate they are becoming more prevalent. “From a biochemical point of view, the prevalence of these emerging isomers has unknown biological consequences and studies aimed at evaluating their biological relevance are therefore imperative.” he said.

“For the plant they seem to give it the capacity to withstand stress better. So does that mean that geometrical isomers are an evolutionary strategy to maximise the plant’s defence, a strategy to fight pathogens – we still don’t know this fully.”

“We also don’t know what their potential functions may be in humans but our preliminary results show some positive biological attributes associated with these compounds.”

Hiding in plain site

Part of the initial challenge was in identifying these sunlight-induced isomers as opposed to the tens of thousands of naturally occurring ones.

“Using mass spectrometry we have found that the newly formed ones bind to metal better than the natural ones – this gives a simple, reliable means of distinguishing. So via computational modelling and mass spectrometry we can identify newly formed isomers with a high degree of confidence. Now we want to understand whether they have good or bad attributes.”

Madala and his colleagues will therefore look at exposing plant extracts to UV-light of different intensities. These extracts will be analysed with the aid of LC-MS and multivariate statistical modelling of this data will be carried out to unearth the effect of the UV-light on the chemistry of these metabolites. The same extracts will then be evaluated for their biological activities to establish their pharmacological relevance. They will also look at the effect of enhanced light exposure on plants that usually grow underground to see the effect on their metabolite production.

“The study is expected to showcase the photo-catalytic properties of UV-light as a feasible approach to generate photo-switchable drugs with enhanced pharmacological activities,” he said.

“We are developing studies to try and see if we can artificially change the metabolite production of the whole plant. We believe such isomers could be attractive candidates for smarter, more rationalised drug development with a wider synergistic effect and polarity range. Slight changes could result in smarter drugs and preventive therapies working in places in the body they don’t currently, where viruses, bacteria and cancers are hiding.”

Michelle Galloway: Part-time media officer at STIAS
Photograph: Nel-Mari Loock



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