An improved bioproduction system for proteins and 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.
While microorganisms have proven to be exceptionally powerful for manufacturing certain molecules, many are not easily produced in high yields. There is particular interest in platforms that are able to respond rapidly to new disease threats, for example, the production of vaccines. 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.
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 identifying genes expressed by the plant in response to the presence of foreign molecules that are deleterious to heterologous bioproduction of small molecules and are engineering new lines of Nicotiana benthamiana, a relative of tobacco from Northern Australia, to improve the production of small molecules. This work is adding to our knowledge of the complex metabolism of plants, helping us to understand how it responds to perturbation.