Deep in the soil of Ghana are compounds that could help scientists to understand a group of naturally-occurring chemicals said to have cancer-fighting properties. An international research team led by the University of Aberdeen, Wuhan University, China and University of Ghana, Legon, has discovered the new compounds and identified the compound legonmycins, named for the region in Ghana in which it was found (https://www.dddmag.com/news/2015/08/research-team-takes-step-forward-understanding-cancer-fighting-compounds?et_cid=4738815&et_rid=45505806&location=top).
Legonmycins A and B are part of a group of naturally occurring alkaloids based on the pyrrolizidine backbone. Pyrrolizidine alkaloids (PAs) are produced mainly by plants as a defense mechanism against insect pests and herbivores. They have been used by humans since ancient times for therapeutic and recreational purposes. While more than 660 plant pyrrolizidines are known, only as many as 10 bacteria PAs have been characterized. Recent studies have demonstrated that PAs have pharmaceutical importance as anti- tumor and anti-inflammatory agents, but their biosynthetic origins had been poorly understood (https://www.modernghana.com/news/634565/1/university-of-ghana-discovers-cancer-fighting-agen.html).
The research team has attempted to establish how and why these compounds occur. According to Dr Hai Deng from the University of Aberdeen, the benefit of their effort, which is published in Angewandte Chemie Int. Ed. is two-fold. It elaborates on current understanding of this important group of alkaloids, which is critical if the full pharmaceutical potential of this material were to be realized, and the newly discovered compound could eventually be used in the development of new drug-like treatments.
Dr Kwaku Kyeremeh, a lecturer from the chemistry department, University of Ghana, explained, “Natural products have been known to have therapeutic benefits for centuries and play an important role in the development of new anti-tumor and anti –inflammatory agents. However, in their natural state, they are often toxic to human health or are not potent enough to deliver any advantage.
Dr Yi Yu, an associate professor from Wuhan University, added, “It can also be difficult to generate the compounds in sufficient quantities and this is where chemistry and synthetic biology is needed to generate what is known as an ‘analogue’ – a modified version suited to human health.”
According to Dr Deng, “The generation of these analogues relies first on determining the genome sequence of the compounds and then working out how they can be synthesized. We have made a breakthrough in understanding this with the compound we discovered called legonmycins and this has implications for our understanding of other bacterium-derived compounds within this family which are known to have cancer-fighting properties.”
Dr Deng said the next stage would be to look at how the code the researchers have unraveled in legonmycins can be applied more widely for the generation of potent analogues with the potential to treat cancer and other diseases. The ultimate goal is to create many other analogues using synthetic biology.