Revisited After 50 Years: The “Stereochemical Interpretation of the Biogenetic Isoprene Rule for the Triterpenes”

Abstract

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Synthesis of arborane triterpenols by a bacterial oxidosqualene cyclase

“…This substitution, S725F (homologous to H. sapiens LAS residue S699), is two amino acid residues downstream of our M. alcaliphilum LAS N717Y substitution, which enabled the synthesis of pentacyclic triterpenoids. Even though the β-amyrin synthase differs from lanosterol and arborinol synthases in that it cyclizes oxidosqualene in the CCC rather than the CBC conformation (5,7), these data demonstrate that this region is critical to the formation of the E ring in both plant and bacterial triterpenoid synthases. Thus, our studies together underscore the functional diversity of triterpenoid synthases and demonstrate the potential for engineering the specificity of these cyclases to synthesize novel triterpenoids and other secondary metabolites.…”

“…A few bacteria have been shown to produce sterols (8), however, the most common bacterial cyclic triterpenoids are the pentacyclic hopanoids, which are thought to function as "sterol surrogates" in bacterial membranes (9,10). Although the majority of interest in cyclic triterpenoids stems from their essential physiological roles and unique enzymatic biosynthesis (5,7,11), these lipids are also significant from a geological perspective. Cyclic triterpenoids are quite recalcitrant and, as a result, are well preserved in sedimentary rocks and can serve as geological biomarkers that link organisms to environments deep in Earth's history (12).…”

“…Cyclic triterpenoid lipids are synthesized by cyclization of a 30-carbon acyclic isoprenoid substrate through a series of carbocation intermediates in the central cavity of a terpene cyclase (class II) enzyme (11,22). These enzymes can be distinguished based on three general characteristics: the use of squalene or oxidosqualene as the initial substrate, the conformation of the acyclic substrate in the more energetically favorable all-chair (CCC) versus the more strained chair−boat−chair (CBC or B boat), and the total number and size of the rings generated in the final product (e.g., tetracyclic sterols versus pentacyclic hopanoids and isoarborinol) (5,7,23). Hopanoid synthases fold squalene into the CCC conformation and generate a pentacyclic structure (11,24), whereas sterol synthases cyclize oxidosqualene in the CBC conformation and generate a tetracyclic structure (25).…”

“…An arborinol synthase represents a unique combination of these characteristics. It is similar to a sterol cyclase in that it cyclizes oxidosqualene in the CBC conformation (6,7,23) but differs in that its final product Significance Polycyclic lipids produced by bacteria and eukaryotes can be preserved in sedimentary rocks for millions of years. These ancient lipids can function as "molecular fossils" or biomarkers that can inform us about the types of organisms and environments on early Earth.…”

Terpenos, aromas e a química dos compostos naturais

“…Apesar de apresentarem diferenças estruturais entre si, todos os terpenos/terpenoides são basicamente estruturados em blocos de cinco carbonos -unidades de isopreno (C 5 H 8 ) -normalmente, ligadas entre si pela ordem "cabeça-a-cauda" (ligação 1-4) (Figura 2), o que caracteriza a chamada "regra do isopreno" (Lommis & Croteau, 2014;Eschenmoser & Arigoni, 2005 ("ligações cruzadas"). Esta derivação da estrutura química em unidades de cinco carbonos, comum aos terpenos, é resultado da sua origem bioquímica, já que todos os seus carbonos são provenientes do isopentenil pirofosfato (IPP) ou de seu isômero dimetilalil pirofosfato (DMAPP).…”