Chemoenzymatic( S)-nicotine: Redefining nicotine production
myosmine( S)-nornicotine( S)-nicotine
Figure 1- Chemoenzymatic process to( S)-nicotine and indicative enzyme structure
Nicotine, a widely used alkaloid in pharmaceuticals and smoking cessation products, has traditionally been derived from the tobacco plant— a resource-intensive crop with a high environmental footprint.
Tobacco-based nicotine extraction consumes vast amounts of water and contributes to CO 2 emissions. The extracted material is of low purity with the presence of related alkaloids and variable amounts of carcinogenic tobacco-specific nitrosamines( TSNAs). Although such extracted nicotine can be purified, to do so to a high degree is expensive.
But what if nicotine production could break free from its reliance on offshore cultivation? Zanoprima Lifesciences has achieved exactly that with SyNic *, produced via a groundbreaking cost-competitive chemoenzymatic process that selectively generates( S)-nicotine of inherently high chemical purity( typically 99.9 %) and high enantiomeric excess(> 99 %).
The above innovation was made possible through a strategic collaboration between Zanoprima and Enzymicals, showing the power of biocatalysis in enabling industrial
scale production. Then, by further collaboration with Imperagen, a UKbased leader in AI-driven enzyme design and synthetic biology, the two companies enhanced the biocatalyst’ s performance, optimising the process even further
From tobacco fields to precision biocatalysis
With increasing demand for a purer, cleaner, and a more sustainable nicotine alternative, Zanoprima sought to develop an enzyme-based production route that eliminates the harmful tobacco-specific impurities, such as nitrosamines, harsh flavours and unwanted( R)-nicotine enantiomer. Additionally, this would provide for full traceability of the materials’ origins and processing.
Headquartered in Germany, Enzymicals was selected by Zanoprima to find a good enzyme for its route to( S)-nicotine in which myosmine, made from nicotinic acid is first converted into the chiral intermediate( S)-nornicotine( Patent EP3653617B1, US10913962B2). Leveraging its deep expertise in imine reductases( IREDs), Enzymicals identified an enzyme with unmatched selectivity and an adequate productivity.
Through process optimisation and scale-up, Enzymicals ensured a seamless transition from lab-scale research to commercial production, delivering a robust, industrially viable biocatalytic process that met high-efficiency, sustainability and regulatory standards.
“ With our expertise in enzyme-driven industrial processes, Enzymicals successfully enabled the commercial-scale chemoenzymatic production of nicotine. This project is a testament to how targeted biocatalysis can revolutionise fine chemicals manufacturing while advancing sustainability”
Dr David Liese, CEO, Enzymicals
78 SPECIALITY CHEMICALS MAGAZINE ESTABLISHED 1981