6OH6

Crystal structure of (E)-biformene synthase LrdC from Streptomyces sp. strain K155 in complex with Mg and PPi

Replaces:  5A0J

Summary for 6OH6

• Entry DOI: 10.2210/pdb6oh6/pdb
• Descriptor: Labdane-related diterpene synthase, PYROPHOSPHATE, MAGNESIUM ION, ... (6 entities in total)
• Functional Keywords: bioactive natural products, biformene, diterpene synthase, labdatriene, lyase
• Biological source: Streptomyces sp.
• Total number of polymer chains: 1
• Total formula weight: 37901.45

Authors

Centeno-Leija, S.,Serrano-Posada, H. (deposition date: 2019-04-04, release date: 2019-04-17, Last modification date: 2024-04-03)

Primary citation

Centeno-Leija, S.,Tapia-Cabrera, S.,Guzman-Trampe, S.,Esquivel, B.,Esturau-Escofet, N.,Tierrafria, V.H.,Rodriguez-Sanoja, R.,Zarate-Romero, A.,Stojanoff, V.,Rudino-Pinera, E.,Sanchez, S.,Serrano-Posada, H.
The structure of (E)-biformene synthase provides insights into the biosynthesis of bacterial bicyclic labdane-related diterpenoids.
J.Struct.Biol., 207:29-39, 2019

PubMed Abstract: The labdane-related diterpenoids (LRDs) are a large group of natural products with a broad range of biological activities. They are synthesized through two consecutive reactions catalyzed by class II and I diterpene synthases (DTSs). The structural complexity of LRDs mainly depends on the catalytic activity of class I DTSs, which catalyze the formation of bicyclic to pentacyclic LRDs, using as a substrate the catalytic product of class II DTSs. To date, the structural and mechanistic details for the biosynthesis of bicyclic LRDs skeletons catalyzed by class I DTSs remain unclear. This work presents the first X-ray crystal structure of an (E)-biformene synthase, LrdC, from the soil bacterium Streptomyces sp. strain K155. LrdC was identified as a part of an LRD cluster of five genes and was found to be a class I DTS that catalyzes the Mg-dependent synthesis of bicyclic LRD (E)-biformene by the dephosphorylation and rearrangement of normal copalyl pyrophosphate (CPP). Structural analysis of LrdC coupled with docking studies suggests that Phe189 prevents cyclization beyond the bicyclic LRD product through a strong stabilization of the allylic carbocation intermediate, while Tyr317 functions as a general base catalyst to deprotonate the CPP substrate. Structural comparisons of LrdC with homology models of bacterial bicyclic LRD-forming enzymes (CldD, RmnD and SclSS), as well as with the crystallographic structure of bacterial tetracyclic LRD ent-kaurene synthase (BjKS), provide further structural insights into the biosynthesis of bacterial LRD natural products.

PubMed: 30981884
DOI: 10.1016/j.jsb.2019.04.010

Experimental method

X-RAY DIFFRACTION (2.07 Å)