Taking innovative action on industrial organic synthesis Toxic materials are used in most industrial chemical processes, but researchers are looking to develop greener alternatives using biocatalysis. Researchers in the CarbaZymes project are drawing inspiration from the natural world to develop more sustainable processes, work which will have a positive impact on both society and industry, as Professor Wolf-Dieter Fessner explains
Engineering novel enzymes using advanced bioinformatics tools and screening for optimized catalyst properties.
The process of assembling simple fragments to build large, complex products by connecting carbon-carbon bonds (C–C bonds) is an essential technology at the heart of industrial organic synthesis. The current methods for creating C–C bonds are heavily reliant on metal catalysis, particularly involving rare noble metals, such as palladium or rhodium complexes. Ores for these materials can only be mined in a few locations across the world, an activity resulting in very significant pollution. “These mining sites are among the most polluted places on earth, causing global environmental damage via release of millions of tonnes of toxic waste into the air every year,” explains Professor Wolf-Dieter Fessner. “Many traditional chemical operations not only involve the use of such toxic materials, but also are very energy-intensive, as extremely high temperatures are generally required. It’s sometimes not only necessary to operate under such harsh conditions, but also to use activated reagents - the manufacture of these compounds themselves results in the accumulation of significant amounts of environmentally unfriendly waste materials.” As the Principal Investigators of the CarbaZymes project, Professor Fessner is exploring an alternative approach to forming C–C bonds by using enzymes from nature as efficient eco-friendly catalysts. The work of Professor Fessner and his colleagues in the project is largely motivated by concerns 22
around the sustainability of current methods. “A general greening of industrial processes would be very much in the interests of European citizens, and those beyond of course. There’s a strong trend in the chemical and pharmaceutical industries nowadays towards developing more sustainable biocatalytic processes,” he stresses. This is a topic that lies at the heart of the CarbaZymes project’s agenda. Whereas with traditional chemical methods product selectivity is difficult to achieve, biochemical catalysts for C–C bond formation synthesize the same products chemo-, regio- and stereo-selectively with exquisite precision, leading to the formation of chiral molecules containing up to two new adjacent chiral centres of known configuration. Enzymes can also achieve unparalleled rate acceleration under mild temperatures and pressures in a near neutral aqueous reaction media,
Sensitive high-throughput screening of enzyme arrays to rapidly identify novel enzyme activities..
thereby consuming much less energy while eliminating the use of hazardous solvents and reagents, with concomitant minimisation of waste and cost. “The ultimate ideal is to utilise renewable resources as starting materials. For example, taking compounds from nature, processing them with the aid of enzymes under sustainable conditions, and producing materials that can be recycled,” says Professor Fessner. A number of hurdles remain, however, before such a circular bioeconomy can become a reality. The research required is multi-disciplinary in nature, with Professor Fessner and his colleagues aiming to develop an unprecedented platform of novel C–C bond forming enzymes, in particular a specific class called lyases. “Specifically we’re looking at aldol reactions, which are actually well known to the organic chemist. Man’s efforts, however, pale into insignificance when compared to those of nature. Over millions of years, nature has evolved lyases for the efficient synthesis of a huge variety of different target compounds, many of which are totally unknown” he continues. “However, most such enzymes exhibit strict specificity for highly functionalised natural compounds, and are thus unlikely to be of immediate interest to industry, where low-functionalised substrates are the norm.” “It was actually with this challenge in mind that the CarbaZymes consortium
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