Rare plant compound subject of novel industrial-scale production method
Plant-derived diterpenoids, which used in food ingredients and fragrances, are a structurally diverse class of natural compounds, widely distributed in nature but relatively underutilised in industry.
Plants provide the major source of these chemicals and present a source of potentially new applications. An example of a diterpene compound is steviol glycoside, the sweet molecules responsible for the sweetness found in stevia.
The laborious process of extracting pure compounds from natural sources on an industrial scale is the main limitation. Synthetic routes remain commercially impracticable due to low efficiency.
Now, a collaborative study between scientists at the Swiss biotech firm Evolva and the University of Copenhagen has detailed a technique that mimics the recombination of diterpene biosynthesis in plants, resulting in 51 functional combinations of Class I and Class II diterpensynthases, 41 of which are novel.
“It’s not just about scale,” said Stephan Herrera, vice president of strategy and public affairs for Evolva. “We think there are a number of positives on offer like taste, functionality, and sustainable sourcing.”
The technique demonstrated selective production of over 50 diterpene skeletons, including natural variants and new chemically distinctive counterparts.
Production technique
It uses a two-step enzyme reaction, overseen by a multifunctional class of enzymes known as diterpene synthases (diTPSs).
After a series of enzyme reactions, which produce a series of intermediate compounds, diterpene skeletons are formed. These skeletons are then subject to a number of chemical reactions that introduce chiral centres, the basis of the molecule’s biological activity.
The scientists were able to achieve scalable biotechnological production for four industrially relevant targets in engineered strains of Saccharomyces cerevisiae, a species of yeast that has been instrumental to winemaking, baking and brewing.
“This pathway enables access to these diterpenoids and their specific and novel chemistry, which often defines their value to the industry,” the study said.
“Our approach meets a long-standing desire for control over the stereochemical configuration of synthesized diterpenes, which remains a challenge in formal chemical synthesis.”
Diterpenes in industry
As well as steviol glycosides, diterpenes are used in fragrance applications. Ambroxide, widely known by the brand name Ambroxan, is a naturally occurring terpenoid used in perfumery for creating fragrances and as a fixative. Small amounts can be used as flavouring in food.
In the pharmaceutical industry, taxol is one of the best known examples of a commercially available product based on a diterpenoid.
Source: Angewandte Chemie International Edition
Published online ahead of print, DOI: 10.1002/anie.201510650
“Expanding the Landscape of Diterpene Structural Diversity through Stereochemically Controlled Combinatorial Biosynthesis.”
Authors: Dr. Johan Andersen-Ranberg et al.
