Diterpene Biosynthesis in Catenulispora acidiphila: On the Mechanism of Catenul‐14‐en‐6‐ol Synthase

Abstract

A new diterpene synthase from the actinomycete Catenulispora acidiphila was identified and the structures of its products were elucidated, including the absolute configurations by an enantioselective deuteration approach. The mechanism of the cationic terpene cyclisation cascade was deeply studied through the use of isotopically labelled substrates and of substrate analogues with partially blocked reactivity, resulting in derailment products that gave further insights into the intermediates along the cascade. Their chemistry was studied, leading to the biomimetic synthesis of a diterpenoid analogue of a brominated sesquiterpene known from the red seaweed Laurencia microcladia.

Mechanistic Insights into the Formation of the 6,10‐Bicyclic Eunicellane Skeleton by the Bacterial Diterpene Synthase Bnd4

“…Our work supports a mechanistic proposal for the cyclization of the eunicellane skeleton where 1,10‐cyclization precedes 1,14‐cyclization. Similar mechanisms were proposed in the cyclizations of catenul‐14‐en‐6‐ol and hydropyrene, although 1 is not formed by the bacterial di‐TSs catenul‐14‐en‐6‐ol synthase (CaCS) or hydropyrene synthase (HpS) [40, 41] . In fact, Bnd4 shares only 23 % identities with both CaCS (52 % coverage) and HpS (85 % coverage).…”

Hot off the Press

“…A novel diterpene synthase from Catenulispora acidiphila that generates products such as the 6,6,6-tricyclic diterpene alcohol catenul-14-en-6-ol 19 has been identified. 16 Isotopic labelling experiments have confirmed the absolute configuration of the new diterpenes and revealed the mechanism of the cationic terpene cyclisation cascade. Identification of the biosynthetic gene clusters of three tropolone sesquiterpenoids (TS) such as pycnidone 20 has allowed a synthetic biology study in which the genes from these clusters have been recombined in the fungal host Aspergillis oryzae NSAR1.…”

Discovery and Biosynthesis of a Structurally Dynamic Antibacterial Diterpenoid

“…Recently,a6,10-bicyclic intermediate with the same absolute configuration of 2 was proposed in the cyclization mechanism of catenul-14-en-6-ol synthase (CaCS), using comprehensive isotopic labeling experiments, benditerpetriene,h owever, is not formed by CaCS. [25] Bnd4 and CaCS only share 23 %s equence identity with 52 % coverage.T hese data, taken together, support the functional assignment of Bnd4 as ap roduct-specific benditerpe-2,6,15triene synthase.…”