Sustainable (-)-ambrox production: chemistry meets biocatalysis
(-)-Ambrox, the most prominent olfactive component of ambergris is one of the most widely used biodegradable fragrance ingredients. It is traditionally produced from the diterpene sclareol, transformed into (-)-ambrox by classical synthetic chemistry. The availability of the new feedstock farnesene opened new pathways to homofarnesol for (-)-ambrox production. Alicyclobacillus acidocaldarius Squalene Hopene Cyclase (SHC) was evolved by means of random mutagenesis to biocatalysts suitable for (-)-ambrox production at industrial scale. Amino acid mutations responsible for improving homofarnesol cyclization were identified. Enzyme evolution together with process optimization produced improved SHC variants allowing for the diastereo- and enantioselective conversion of up to triple digit gram per liter homofarnesol to (-)-ambrox . In parallel, access to the required homofarnesol precursor was investigated. Routes starting from farnesene were developed , delivering efficient processes for homofarnesol and its precursors at multi-ton scale for (-)-ambrox production. This double invention led to a sustainable production of the fragrance ingredient (-)-ambrox as a drop-in quality for AmbrofixTM .
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