7XSI

SdnG, a Diels Alderase catalyzed the formation of norbornene skeleton in Sordarin biosynthetic pathway

Replaces:  7XFK

Summary for 7XSI

• Entry DOI: 10.2210/pdb7xsi/pdb
• Descriptor: Sordarin/hypoxysordarin biosynthesis cluster protein G (2 entities in total)
• Functional Keywords: pericyclase, diel alderase, biosynthetic protein
• Biological source: Sordaria araneosa
• Total number of polymer chains: 8
• Total formula weight: 145227.36

Authors

Zhang, B.,Ge, H.M. (deposition date: 2022-05-14, release date: 2022-12-28, Last modification date: 2023-10-18)

Primary citation

Liu, S.H.,Sun, J.L.,Hu, Y.L.,Zhang, L.,Zhang, X.,Yan, Z.Y.,Guo, X.,Guo, Z.K.,Jiao, R.H.,Zhang, B.,Tan, R.X.,Ge, H.M.
Biosynthesis of Sordarin Revealing a Diels-Alderase for the Formation of the Norbornene Skeleton.
Angew.Chem.Int.Ed.Engl., 61:e202205577-e202205577, 2022

PubMed Abstract: Sordarin (1) is a fungal diterpene glycoside that displays potent antifungal bioactivity through inhibition of elongation factor 2. The structures of sordarin and related compounds feature a highly rearranged tetracyclic diterpene core. In this study, we identified a concise pathway in the biosynthesis of sordarin. A diterpene cyclase (SdnA) generates the 5/8/5 cycloaraneosene framework, which is decorated by a set of P450s that catalyze a series of oxidation reactions, including hydroxylation, desaturation, and C-C bond oxidative cleavage, to give a carboxylate intermediate with a terminal alkene and a cyclopentadiene moiety. A novel Diels-Alderase SdnG catalyzes an intramolecular Diels-Alder (IMDA) reaction on this intermediate to forge the sordarin core structure. Subsequent methyl hydroxylation and glycosylation complete the biosynthesis of sordarin. Our work discloses a new strategy used by nature for the formation of the rearranged diterpene skeleton.

PubMed: 35701881
DOI: 10.1002/anie.202205577

Experimental method

X-RAY DIFFRACTION (2.7 Å)