With 12,000+ known structures, diterpenoids are a prime example of bio-active natural products produced by plants. Many are used as highly valuable pharmaceuticals, fragrances, natural plant growth promoters, food ingredients such as flavors or as colorants and spices.
Unfortunately, they are typically produced in minute amounts in plants and their structural complexity render them difficult to prepare from fossil resources using organic chemical synthesis. We have developed an integrated biochemical and functional genomics bio-sustainable production including targeted metabolomics and single cell-type transcriptome studies to identify the genes encoding a desired pathway. The functional parts identified also enabled combinatorial assembly of new-to-nature diterpenoid pathways. The entire pathway for forskolin was elucidated. Forskolin is a cyclic AMP booster approved for treatment of glaucoma but also used as a weight loss aid. The forskolin pathway is being used as test model system for large scale light driven production of high value diterpenoids following targeting of the P450s to the
thylaloid membrane and using cyanobacteria or moss as photosynthetic production hosts grown in contained photo-bioreactors. Our results pave the way for development of other large scale light driven biotechnological production systems and for synthetic biology approaches for rational expansion of diterpenoid chemical diversity.


Keynote speaker