# Telescoping a Prenyltransferase and a Diterpene Synthase to Transform Unnatural FPP Derivatives to Diterpenoids

**Authors:** Henry Struwe, Heng Li, Finn Schrödter, Laurent Höft, Jörg Fohrer, Jeroen S. Dickschat, Andreas Kirschning

PMC · DOI: 10.1021/acs.orglett.4c01670 · Organic Letters · 2024-07-08

## TL;DR

Scientists used two enzymes to create new diterpenoids from modified FPP, resulting in unique chemical structures not seen before.

## Contribution

The study reports the first observation of a 1,12-terpene cyclization and the creation of new diterpenoid structures.

## Key findings

- Four new diterpenoid products were synthesized using a prenyltransferase and a diterpene synthase.
- Three new cyclododecane cores and a macrocyclic ether were produced from non-natural FPP derivatives.
- A 1,12-terpene cyclization was observed for the first time through a shift in the double bond position.

## Abstract

New diterpenoids are accessible from non-natural FPP
derivatives
as substrates for an enzymatic elongation cyclization cascade using
the geranylgeranyl pyrophosphate synthase (GGPPS) from Streptomyces
cyaneofuscatus and the spata-13,17-diene synthase (SpS) from Streptomyces xinghaiensis. This approach led to four new
biotransformation products including three new cyclododecane cores
and a macrocyclic ether. For the first time, a 1,12-terpene cyclization
was observed when shifting the central olefinic double bond toward
the geminial methyl groups creating a nonconjugated 1,4-diene.

## Linked entities

- **Chemicals:** FPP (PubChem CID 445713), cyclododecane (PubChem CID 9268)
- **Species:** Streptomyces cyaneofuscatus (taxon 66883), Streptomyces xinghaiensis (taxon 1038928)

## Full-text entities

- **Genes:** GGPS1 (geranylgeranyl diphosphate synthase 1) [NCBI Gene 9453] {aka GGPPS, GGPPS1, MDHLO, MUDHLOV}, PDSS1 (decaprenyl diphosphate synthase subunit 1) [NCBI Gene 23590] {aka COQ1, COQ10D2, COQ1A, DPS, SPS, TPRT}
- **Species:** Streptomyces cyaneofuscatus (species) [taxon 66883], Streptomyces xinghaiensis (species) [taxon 1038928]

## Full text

_Full body text omitted from this summary view._ Fetch the complete paper as Markdown: https://tomesphere.com/paper/PMC11267608/full.md

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11267608/full.md

## References

32 references — full list in the complete paper: https://tomesphere.com/paper/PMC11267608/full.md

---
Source: https://tomesphere.com/paper/PMC11267608