2015 Nobel prize recognises importance of research into medicinal compounds made by plants and microbes.

From the John Innes Centre

Earlier this month the Nobel Prize for physiology and medicine was awarded to three scientists who pioneered the development of new drugs from plants and microbes, and in doing so, went on to save millions of lives.

Chinese scientist, Professor Youyou Tu, received half the Nobel prize for developing artemisinin, a drug from the wormwood plant which gave the world a desperately needed new therapy for treatment of malaria.

Professors Satoshi Omura and William Campbell received a quarter of the prize each for the development of ivermectin, a drug made by a bacterium called Streptomyces avermitilis. Ivermectin was originally intended to tackle parasitic infections in animals, but it also proved to be extremely effective as a simple and life-changing treatment for the human parasitic infections which cause river blindness and elephantiasis.

The John Innes Centre is a world leader in this area of science. Scientists in the Plant and Microbial Metabolism programme aim to understand how plants and microbes make diverse natural compounds, and to apply this knowledge to develop new therapeutics that can improve human and animal health. Two relevant examples of current JIC research are the continuing discovery of potential new antibiotics made by species of the bacterium Streptomyces, and the discovery of how the anti-cancer drug vincristine is made by the Madagascar periwinkle plant.

Streptomycetes and antibiotics

Streptomycetes are soil-dwelling bacteria that give rise to half of the antibiotics used in human and veterinary medicine and agriculture. Ivermectin is one of the best known examples; another is streptomycin for which Professor Selman Waksman was awarded the Nobel Prize for Medicine in 1952. Streptomycetes also produce compounds that are used as anti-cancer agents, herbicides and other pharmacologically active chemicals such as immuno-suppressants, and several enzymes that are important to the food industry. 

Following the huge advances in understanding antibiotic production by Streptomyces species stemming from the research of Professor David Hopwood at JIC from the 1960s onwards, Professor Merv Bibb and Dr Barrie Wilkinson and Dr Andy Truman are working to discover new compounds made by Streptomyces and related bacteria. Their discoveries build on the pioneering work of Omura, Campbell, Waksman, Hopwood and others, and are needed more urgently than ever in the face of the dwindling effectiveness of current antibiotics for many major diseases.

Fortunately, advanced methods of sequencing bacterial genomes have now revealed that these bacteria have the genetic capacity to make many diverse compounds with unexplored structures and properties. There is thus huge untapped potential for the discovery of new antibiotics. The John Innes researchers are using combinations of genetics, bioinformatics, chemistry and molecular biology to pinpoint and characterise new compounds of potential value, and to engineer the production of large amounts of these compounds for tests of their antibiotic properties. The researchers collaborate with other organisations and pharmaceutical companies to ensure that new compounds can be rapidly developed into drugs if they show therapeutic potential. 

The Madagascar Periwinkle (Catharanthus Roseus) - The plant that makes vincristine

Madagascar periwinkle and anti-cancer drugs

The Madagascar periwinkle plant produces rare complex compounds that are used as anticancer therapies. Vincristine, for example, is important for the treatment of several cancers. The drug has to be purified from the plant, and as a result it is very expensive and in short supply. Professor Sarah O’Connor is working with collaborators in Europe and the USA to discover how this and related compounds are made in the plant. Her discoveries will lead to better production methods for the anticancer compounds, and the development of novel, related compounds which may have new or enhanced therapeutic properties. She recently engineered yeast cells to produce a precursor to vincristine, using genes from the periwinkle plant. This development opens up the possibility of cheap, large scale production of vincristine in the future.

Many species of plants in addition to the Madagascar periwinkle produce valuable drugs. The antimalarial drug artemisinin discovered by Professor YouYou Tu in the wormwood plant is an outstanding example. Quinine, the original antimalarial therapy, comes from a South American tree, and plants also produce morphine, atropine and a host of other drugs in common use. JIC makes major contributions to the discovery of new therapeutic compounds from plants. As for bacteria, new information about plant genomes shows us that plants have a huge capacity for the production of potentially valuable molecules that have not yet been characterised. Genomic information also helps us to discover the compounds responsible for the therapeutic properties of plants used in traditional medicines. The research of Professors Sarah O’Connor, Anne Osbourn, Cathie Martin, Rob Field and George Lomonossoff and Dr Paul O’Maille is leading to the discovery of new compounds and how they are made in plants, to the synthesis of altered versions of therapeutic compounds expected to have novel properties, and to methods for engineering large scale production of plant-derived therapeutic compounds.