University of Ghana, University of Aberdeen and Wuhan University in
China has discovered a set of new alkaloids from a novel Ghanaian
microorganism
An international research team
from the University of Ghana, University of Aberdeen and Wuhan
University in China has discovered a set of new alkaloids from a novel
Ghanaian microorganism which have great potential as future microbial
and cancer fighting agents.
Dr. Kwaku Kyeremeh,
a lecturer at the University of Ghana’s Department of Chemistry in
collaboration with other researchers have identified for the first time,
the compounds Legonmycins A and B, named after Legon, a suburb in
Ghana, where the producing microorganism was found and isolated.
Legonmycins
A and B belong to a group of naturally occurring alkaloids based on the
pyrrolizidine backbone. Pyrrolizidine alkaloids (PAs) are produced
mainly by plants as a defence mechanism against insect pests and
herbivores but, have been used by humans since ancient times for
therapeutic and recreational purposes. Interestingly, while over 660
plant pyrrolizidines are known, only up to 10 bacteria PAs have been
characterized.
More recent studies have shown PAs
to have pharmaceutical importance as anti- tumour and anti-inflammatory
agents but, their biosynthetic origins remained poorly understood until
now.
Dr. Kwaku Kyeremeh, Dr. Hai Deng, Professor
Yi Yu and their colleagues, solved the mystery behind the amino acid
composition and other biosynthetic precursors involved in the
biosynthesis of bacteria PAs. Using genome analysis and identification
of gene clusters, they identified Legonmycins as originating from non-
ribosomal peptide synthetases. Inside the lgn gene cluster, a
talented solo LgnC enzyme was identified and found to catalyse an
unprecedented series of chemical reactions in the final steps of the
biosynthesis of the Legonmycins.
Dr Hai Deng, from
the University of Aberdeen, said the benefit of their work, which is
published in the top international journal Angewandte Chemie Int. Ed. and
featured as the back cover of the journal, is two-fold. “It moves on
current understanding of this important group of alkaloids - an
essential step forward if the full pharmaceutical potential of these
substances are to be realised.
The newly
discovered compounds could themselves one day be used in the creation of
new drug treatments, he said. Dr. Deng further said that, the
generation of these analogues depend first on determining the genome
sequence of the compounds and then working out how they can be
biosynthesised.
According to Dr. Yi Yu, an
Associate Professor from Wuhan University, in order to address the
problem of resupply, the current research is a great step forward to our
ability to use synthetic biology to generate what are known as
analogues which are modified versions of the original alkaloids either
from plants or microbes but, much suited to human health.
One
of the researchers, Dr. Kwaku Kyeremeh, a Lecturer at the University of
Ghana’s Department of Chemistry said that even though Ghana represents
one of the world’s biodiversity rich hotspots until recently, very
little research had been conducted on the country’s flora and fauna.
Different accounts of some work on plants, he added, exist but the
identification of natural product compounds from microbes is completely
new.
Dr. Kyeremeh believed that, Ghana has a
large number of microbial talents which future research must identify
and isolate and noted that the results represent the ultimate goal for
this area and type of research and concluded that the current findings
are an important step forward to achieving this goal.
The research was sponsored by the Leverhulme Trust and the Royal Society’s Africa Award.
