CAS Researchers Identify Plant Sesterterpene Synthases and Their Functional Products

The C25 sesterterpenoids, derived from five isoprene units, are widely distributed in marine organisms, terrestrial fungi, lichens, higher plants, insects, etc. Many possess intriguing skeletons and exhibit interesting bioactivities. However, sesterterpenoids only constitute a relatively small group among terpenoids and their genetic and molecular bases for biosynthesis have seldom been investigated. So far, only several sesterterpene synthases (sesterTPSs) mainly from fungi have been reported. Interestingly, they are responsible for the biosynthesis of a series of sesterterpenes with diverse carbon skeletons. However, to date, sesterTPSs originated from plants have never been disclosed.

Prof. WANG Yong and his colleagues at CAS Center for Excellence in Molecular Plant Sciences, CAS Key Laboratory of Synthetic Biology, Institute of Plant Physiology and Ecology, Chinese Academy of Sciences, with collaboration with Prof. WANG Guodong’s group from Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, identify two plant sesterTPSs in the genome of A. thaliana by coexpressing geranylfarnesyl diphosphate synthase (GFPPS) with the two GFPPS-linked AtTPS18 and AtTPS19 in E. coli, and further obtain their functional products. AtTPS18 is responsible for the biosynthesis of the new tricyclic sesterterpene (+)-thalianatriene (1) with the unique 11-6-5 fused ring system, while AtTPS19 functionally produces the new pentacyclic sesterterpene (-)-retigeranin B (2) with the characteristic 5-5-5-6-5 fused ring system. Interestingly, the trans-angular bond between the (E,E)-?3(20),6,10 cycloundecatriene and the cyclohexane of 1 is rarely formatted at C-2 to C-12, difference from C-1 to C-2 of the known related 11-6-5 carbon skeleton, as in stellata-2,6,19-triene. The structure elucidation of 1 is very challenging, because the conformers in 1 caused by the inversion of the double bonds around the macrocycle are too complex to be discriminated even in -40 oC NMR measured condition. Fortunately, a major epoxy 3 can be purified, which greatly simplifies the conformers. The variable-temp NMR measurement of 3 indicates that 3 exists as an indiscernible mixture of two conformers in CDCl3 solution in a ratio of about 2:1 at or below ordinary probe temp. The most stable conformer 3a is assigned as the UUU (chair-twist) form, while the less populated conformer 3b attributes to the UUD (chair-chair) orientation. X-ray analyses have shown that only the most stable, predominant conformer UUU, exists in the solid state of 3. Finally, the structure of 1 is successfully determined and a plausible biosynthesis mechanism of 1 is proposed. To our knowledge, this is the first report of the discovery of the sesterTPSs from plants and their functional products.

The study entitled “(+)-Thalianatriene and (-)-Retigeranin B Catalyzed by Sesterterpene Synthases from Arabidopsis thaliana” has been published online in Organic Letters on Mar. 29, 2017 (DOI: 10.1021/acs.orglett.7b00586).

The study was supported by Chinese Academy of Sciences, National Natural Science Foundation of China, and Shanghai Committee of Science and Technology.

Article website:
http://pubs.acs.org/doi/abs/10.1021/acs.orglett.7b00586

Sesterterpenes obtained in this study

CONTACT:
WANG Yong, Ph.D.
CAS Center for Excellence in Molecular Plant Sciences
CAS Key Laboratory of Synthetic Biology
Shanghai Institutes for Biological Sciences
Chinese Academy of Sciences
300 Fenglin Road
Shanghai 200032
+86-21-54924295(Tel)
+86-21-54924295(Fax)
email: yongwang@sibs.ac.cn