A synthetic biology and green bioprocess approach to recreate agarwood sesquiterpenoid mixtures

by Sergio Gutiérrez, Sebastian Overmans, Gordon B. Wellman, Vasilios G. Samaras, Claudia Oviedo, Martin Gede, Gyorgy Szekely, Kyle J. Lauersen
Article Year: 2024 DOI: 10.1039/D3GC03708H


Gutiérrez, S., Overmans, S., Wellman, G. B., Samaras, V. G., Oviedo, C., Gede, M., Szekely, G. and Lauersen, K. J. (2024) A synthetic biology and green bioprocess approach to recreate agarwood sesquiterpenoid mixtures. Green Chemistry, doi:10.1039/D3GC03708H


Certain endangered Thymelaeaceous trees are major sources of the fragrant and highly valued resinous agarwood, comprised of hundreds of oxygenated sesquiterpenoids (STPs). Despite growing pressure on natural agarwood sources, the chemical complexity of STPs severely limits synthetic production. Here, we catalogued the chemical diversity in 58 agarwood samples by two—dimensional gas chromatography—mass spectrometry and partially recreated complex STP mixtures through synthetic biology. We improved STP yields in the unicellular alga Chlamydomonas reinhardtii by combinatorial engineering to biosynthesise nine macrocyclic STP backbones found in agarwood. A bioprocess following green-chemistry principles was developed that exploits ‰milking‰ of STPs without cell lysis, solvent—solvent STP extraction, solvent—STP nanofiltration, and bulk STP oxy—functionalisation to obtain terpene mixtures like those of agarwood. This process occurs with total solvent recycling and enables continuous production. Our synthetic-biology approach offers a sustainable alternative to harvesting agarwood trees to obtain mixtures of complex, fragrant, oxygenated STPs.


Agarwood Aquilaria sp. Green algae Chlamydomonas reinhardtii Terpenoids metabolic engineering Green Chemistry organic solvent nanofiltration