Enzymatic Epoxidation of Long-Chain Terminal Alkenes by Fungal Peroxygenases.

Esteban D Babot,René Ullrich,Katrin Scheibner,Carmen Aranda,Angel T Martínez,Martin Hofrichter,Jan Kiebist,Ana Gutiérrez

doi:10.3390/antiox11030522

Abstract

Terminal alkenes are among the most attractive starting materials for the synthesis of epoxides, which are essential and versatile intermediate building blocks for the pharmaceutical, flavoring, and polymer industries. Previous research on alkene epoxidation has focused on the use of several oxidizing agents and/or different enzymes, including cytochrome P450 monooxygenases, as well as microbial whole-cell catalysts that have several drawbacks. Alternatively, we explored the ability of unspecific peroxygenases (UPOs) to selectively epoxidize terminal alkenes. UPOs are attractive biocatalysts because they are robust extracellular enzymes and only require H2O2 as cosubstrate. Here, we show how several UPOs, such as those from Cyclocybe (Agrocybe) aegerita (AaeUPO), Marasmius rotula (MroUPO), Coprinopsis cinerea (rCciUPO), Humicola insolens (rHinUPO), and Daldinia caldariorum (rDcaUPO), are able to catalyze the epoxidation of long-chain terminal alkenes (from C12:1 to C20:1) after an initial optimization of several reaction parameters (cosolvent, cosubstrate, and pH). In addition to terminal epoxides, alkenols and other hydroxylated derivatives of the alkenes were formed. Although all UPOs were able to convert and epoxidize the alkenes, notable differences were observed between them, with rCciUPO being responsible for the highest substrate turnover and MroUPO being the most selective with respect to terminal epoxidation. The potential of peroxygenases for epoxidizing long-chain terminal alkenes represents an interesting and green alternative to the existing synthesis technologies.

Highlights

The importance of epoxides in the chemical industry is based on their high reactivity.There are innumerable reactions that epoxides can undergo with a variety of chemical compounds, which makes them valuable intermediates in organic synthesis
The main purpose of this study was to achieve the epoxidation of long-chain terminal alkenes with enzymes, with fungal peroxygenases, named unspecific peroxygenases (UPOs, EC.1.11.2.1), while taking advantage of the new enzymes discovered in the last few years [24]
Due to the low solubility of alkenes in aqueous media, the cosolvent was the first parameter considered with the testing of different proportions of two solvents commonly used in UPO-catalyzed reactions, i.e., acetone and acetonitrile [31]

Summary

Introduction

The importance of epoxides in the chemical industry is based on their high reactivity.There are innumerable reactions that epoxides can undergo with a variety of chemical compounds, which makes them valuable intermediates in organic synthesis. The epoxidation of alkenes provides oxirane compounds (epoxides) that are essential raw materials in the production of fine chemicals (such as surfactants, epoxy resins, perfumes, plasticizers, pharmaceuticals, agrochemicals, polymers, cosmetics, or paints) and are vital intermediate compounds in organic synthesis [1–3]. In this regard, terminal alkenes are among the most attractive starting materials for chemical synthesis, as they are readily available in large-scale industrial processes and can be obtained on a smaller scale through a number of efficient, catalytic, and highly selective processes [4].

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