Bacterial Diterpene Biosynthesis

Abstract

This Minireview summarises recent developments in the biosynthesis of diterpenes by diterpene synthases in bacteria. It is structured by the class of enzyme involved in the first committed step towards diterpenes, starting with type I diterpene synthases, followed by type II enzymes and the more recently discovered UbiA‐related diterpene synthases. A special emphasis lies on the reaction mechanisms of diterpene synthases that convert simple linear precursors through cationic cascades into structurally complex, usually polycyclic carbon skeletons with multiple stereogenic centres. A further main focus of this Minireview is a discussion of how these mechanisms can be unravelled. Downstream modifications to bioactive molecules are also covered.

A Family of Related Fungal and Bacterial Di‐ and Sesterterpenes: Studies on Fusaterpenol and Variediene

“…During the past few years, a series of structurally related di‐ and sesterterpenes from fungi and bacteria has been identified . These compounds were either isolated from culture extracts, or obtained in genome‐mining approaches by heterologous gene expression in suitable hosts for compound production and isolation or by in vitro incubations of the terpene precursor with the purified enzyme.…”

Enzymatic Synthesis of Methylated Terpene Analogues Using the Plasticity of Bacterial Terpene Synthases

“…During the past decade the genomesequences of many bacteria and fungi becamea vailable, which allowed for the discovery and characterisation of various terpene synthases (TSs). [1][2][3][4][5][6][7] Canonical TSs catalyse the conversion of isoprenoid diphosphates with the general formula (C 5n H 8n+ +1 )OPP including dimethylallyl( DMAPP, n = 1), geranyl (GPP, n = 2), farnesyl (FPP, n = 3), geranylgeranyl (GGPP, n = 4) and geranylfarnesyl diphosphate (GFPP, n = 5) into terpenes. For the larger precursors (n > 1) the products are usually (poly)cyclic and contain multiple stereogenic centres.T he TS-catalysed transformations proceed through substratei onisation by abstraction of diphosphate or by protonation, followed by ac ationic cascade including cyclisation reactions, hydride or proton migrations and skeletal rearrangements.…”

A Straightforward Synthesis of Trideuterated α‐Terpinene for Mechanistic Studies

“…Excellent reviews on various aspects of terpene biosynthesis have highlighted the utility of deuterium labeling in the elucidation of enzymatic reaction mechanisms. [7][8][9] For example, deuterium labeling experiments have been used to elucidate the biosynthetic pathway and establish syn-configuration of tively) with enol triflates to introduce the alkyl substituents on the 1,3-cyclohexadiene backbone. By changing the alkylcuprates, the synthetic approach could serve as a prototype for the synthesis of various 1,4-dialkyl-substituted 1,3-cyclohexadiene derivatives, which could be deuterium-labeled as well, for example for mechanistic studies.…”

“…. GC-MS (EI, 70 eV): m/z (%) 159(9), 158 (100), 142(2), 130(8), 128(7), 114(22), 101(5), 86(39), 74(9), 70(14), 69(23), 58(16), 57(9), 56 (58). Isopropyl-1,4-dioxaspiro[4.5]dec-7-ene (19d).…”