Playing Lego with Terpene Biosynthesis

by Laura Drummond

The smell of orange, lemon and grapefruit, the fresh scent of pine trees during a walk in the forest. The taste of mint in toothpastes, the camphor in pain-relief sprays and even the bitter notes of hops in certain types of beer. Terpenes are more present in our lives than we account for, and yet most of us do not know them by name.

 Terpenes are a class of organic compounds, produced by many different types of organisms, but mostly by plants. They are responsible for severalvolatile aroma compounds that we know, but are also involved in the formation larger molecules likecarotenoids and cholesterol, as well as some very important pharmaceuticals like the anti-malarial drug artemisinin and the anti-cancer medicine taxol.

 When it comes to their biosynthesis, terpenoids always form from two universal precursors: IPP (isopentenyl pyrophosphate) and DMAPP (dimethylallyl pyrophosphate), which are isomers from each other. These two molecules have 5 carbon atomseach, and therefore moleculesdownstream normally have a multiple of 5 carbon atoms in their structures. Terpene biosynthesis is modular, with precursors of fixed size and an almost constant count of carbon atoms, which increases in blocks of five as molecules get bigger

Biosynthesis of terpenoids. The pathways have been conceptually separated into four modules. Image: Vavitsas et al 2018 (CC BY 4.0)

Isopentenyl pyrophosphate (IPP), the universal precursor of Terpenes, and the different precursor molecules that can be formed using a newly discovered methyltransferase.

In our recent paper, published in ACS synthetic biology, we found a way to challenge this ‘multiples of 5’ rule. We discovered an enzyme, hidden in the genome of Streptomyces monomycini, which is able to add one or two methyl groups (CH3) to the universal precursor of terpenes IPP, creating precursors with 6 or 7 carbon atoms in their structure. The discovery brings an additional piece for the biosynthetical pathway of these compounds, which is highly modular and resembles a game of lego. We also demonstrated the formation of larger molecules, with added methyl groups, showing that natural enzymes from the pathway can accept the different versions of IPP, taking advantage of their promiscuity.

 The findings open new possibilities for the biosynthesis of compounds so far unknown, by the addition of a new piece to the lego-like terpene biosynthetical pathway.

 Laura Drummond is a PhD student at the Industrial Biotechnology Department of DECHEMA Research Institute in Frankfurt, Germany. She has a BSc in Biological Sciences from the University of Sao Paulo and a MSc in Entomology from the Luiz de Queiroz College of Agriculture in Brazil.

Twitter:  @drumm34

Linkedin: https://www.linkedin.com/in/laura-drummond-dechema/