Dr Zhenhua Liu

It has been estimated that plants can produce over 1 million specialized metabolites, but we know less than 0.1 % of their biosynthetic pathways. Creative methods are eminently needed to look under the iceberg of largely untapped biosynthetic pathways. As a post-doc from Anne Osbourn group at John Innes Centre, I am employing multidisciplinary approaches across bioinformatics, genetics, and chemistry, to comprehensively understand how and why plants produce this hallmark of specialized metabolites.

I am currently focusing on plants from the Brassicaceae family and systematically studying the function, evolution and biosynthesis of triterpenes from this family. I am in particular interested in pathways encoded by gene clusters. It holds great potential to mine more and novel biosynthetic pathways efficiently. However, how and why plants have evolved BGCs is still a mystery. We are aiming to gain the first understanding of their assembly, patterns of evolution and common features in a systematic fashion. This knowledge can then be used as a template guiding the research of BGCs in other types of compounds and plant families.         

Figure legend: Multidisciplinary approaches to discover new pathways and novel natural compounds. We are using combination of bioinformatics, genetics and chemistry in attempt to decode and recode the largely untapped plant specialized metabolism

Dr Michael Stephenson

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I am a chemist, with a background in natural product total synthesis, medicinal chemistry, and pharmacy. In the Osbourn group we are interested in plant secondary metabolites, and this places us at the very interface between biology and chemistry. I bring expertise in small organic molecule extraction, purification, and structural characterisation. This strengthens the group’s ability to functionally characterise biosynthetic enzymes; something which is important for many areas of research within the Osbourn lab. As such, I am involved in a number of different projects.

My main focus is on the application of transient expression in Nicotiana benthamiana towards the preparative production of high value triterpenes. I have been heavily involved in platform and method development, improving both the efficiency and scalability of procedures used within the group. I have also demonstrated the preparative utility of this platform by producing triterpenes on the gram scale.

As a medicinal chemist I am interested in applying these techniques to engineer chemical diversity, and to explore the structure activity relationships of bioactive triterpenes. I have been involved in isolating and characterising several novel triterpenes structures arising from co-expression of ‘un-natural’ combinations of biosynthetic enzymes. In addition, I have solved the structure of a number of novel and usual triterpene scaffolds, produced by oxidosqualene cyclases under investigation within the group. It would seem that despite the huge number of unique triterpene scaffolds already reported from many decades of natural product isolation, there is still a wealth of novel chemistry to be discovered, and that its discovery can be accelerated by utilising synergy between bioinformatives, synthetic biology, and chemistry.

In addition to my research, I also take a keen interest in public engagement. I have been involved in several outreach events where we attempt to present concepts in synthetic biology and chemistry in an assessable and ‘hands on’ way.    

Dr Hans-Wilhelm Nützmann

Plants produce a wide variety of specialised metabolites. These molecules play key roles in the interaction of plants with their biotic and abiotic environment. In addition to their ecological functions, plant-derived specialised metabolites are major sources of pharmaceuticals and other high-value compounds.

Recently, it was discovered that the genes for the biosynthesis of several major classes of these compounds are physically co-localised in so called ‘gene clusters’ in plant genomes. Such clustering of non-homologous genes contrasts the expected arrangement of genes in eukaryotic genomes. The co-localisation of functionally-related genes enables the formation of fundamentally different mechanisms of gene regulation in comparison to the control of dispersed genes. The purpose of this project is to improve our understanding of the transcriptional control of plant metabolic gene clusters. The focus within OpenPlant will be on chromatin related regulatory processes that govern the expression of gene clusters. By chromatin immunoprecipitation, chromosome conformation analyses and genome engineering we aim to characterise the chromatin environment at gene clusters and its impact on cluster regulation. The findings of this project will open up new opportunities for the discovery and engineering of metabolic pathways using genetic and chemical approaches. They will also underpin synthetic biology-based approaches aimed at refactoring of plant metabolic gene clusters and the development of synthetic traits.