Plant-based Small Molecules

Our new plant synthetic biology platform has the capability to:

  • Reconstitute existing secondary metabolic pathways to allow effective production of high-value compounds
  • Tailor pathways to deliver new or modified molecules with high specificity and efficiency.
  • Generate combinatorial libraries of “new to nature” molecules using only “natural” chemical space
  • Build plant engineering capabilities that integrate new pathways into the genome, and enable the efficient manufacture of the desired molecular species in a “croppable” species

Why synthetic biology is important

  • A wide variety of drug classes, as well as other high-value compounds, are (or are derived from) plant natural products.

  • Many are plant secondary metabolites (compounds produced by the plant that are not directly involved in growth and development; often involved in protecting the plants from pests and disease)

Key applications:

  • Antibiotics
  • Anticancer
  • Sterols
  • Adjuvants
  • Flavourings
  • Fragrances
  • Agrochemicals
  • Industrial lubricants
  • Etc.

Key Challenges

But successful development of a natural-product drug can rapidly lead to issues around supply and sustainability:

Taxol – significant issues with supply of yew bark in early years. Ultimately solved by semi-synthesis and an integrated cultivation program.

QS-21 – pressure growing on Quillaja supply chain after launch of first vaccine (several more products in the pipeline)

Vincristine/vinblastine – low yield (approx. 3 tonnes of leaf material processed per gram vincristine)

Our Key capabilities and approach

  • Pathway elucidation: Using our unique set of bioinformatics and plant transformation tools, Heleogenics will identify the genes responsible for the production of high-value compounds from their natural sources. Our research is done in the Osbourn laboratory, a world leading facility in metabolic pathway elucidation. We use state of the art biological and in-silico techniques there, to identify and validate gene pathway clusters in genomic and transcriptomic data.
  • Pathway reconstruction: Where production from the natural source is impractical or uneconomic, pathways will be engineered into alternative plant species to generate a commercially-viable production platform. Our comprehensive collection of both public-domain and proprietary enzymes is mapped to specific secondary metabolic pathways or biosynthetic functions – which enables us to find the optimal enzyme and species for your needs.
  • Pathway manipulation: Using the rapid prototyping capabilities of the HyperTrans expression system, biosynthetic pathways will be altered to generate variant natural products that may have improved properties. the The HyperTrans™ plant transient-transformation technology  enables the validation of enzyme activities and the rapid testing of gene-set assemblies in plant tissues.

Example 2: Medicinal Chemistry “in planta”

The QS-21 adjuvant precursor, quillaic acid (QA), has been produced in Nicotiana by using transiently-expressed, known enzymes from a variety of plant species to convert the common precursor, β-amyrin, into QA. 

Remarkably, none of the enzymes were from Quillaja, which is the natural source of QS-21.