Improving Plants for Biomanufacturing
Improving the plant ‘production chassis’ for the manufacture of useful, biologically active small molecules.
Plants are the source of a great diversity of biologically active small molecules. A great many natural products found in plants are used as human therapies. However, these chemicals are often found in low abundance or are produced in species that are difficult to mass-cultivate requiring either chemical synthesis or the transfer of the genetic pathway to an alternative biological host in order to produce compounds in sufficient quantities.
Plants have been shown to be capable of efficient expression of therapeutic proteins and secondary metabolites. They are cheap to grow and maintain, mainly requiring just water and light and, in a process commonly known as 'molecular pharming', have been demonstrated to be capable of producing large quantities of proteins, including those used as vaccines in just a few days.
Much work has been done to tailor specific strains of bacteria and yeasts to increase production of compounds. However, to date, little effort has been spent on improving the plant 'production chassis', partly due to a lack of available tools. New technologies are allowing us to take targeted approaches to improving plants to express certain types of molecules.
Heterologous expression can be complicated by the endogenous metabolism of the host, diverting intermediates or performing unwanted modifications of expressed molecules. Much work has been done to tailor specific strains of bacteria and yeasts to increase production of compounds. However, to date, little effort has been spent on improving the plant production chassis, partly due to a lack of available tools. New technologies, such as CRISPR/Cas, have enabled us to take targeted approaches to modifying plant genes. We are using genomics to identify genes expressed by the plant in response to the presence of foreign molecules that are deleterious to the production of proteins and small molecules. We are then engineering new lines of Nicotiana benthamiana, a relative of tobacco from Australia, to improve its ability to produce several valuable small molecules. This work is adding to our knowledge of the complex metabolism of plants, helping us to understand how it responds to perturbation.