Enzymatic cyclization of homofarnesylic acid

A process for the preparation of 3a,6,6,9a-tetramethyldodecahydronaphto[2,1-b]furan (ambroxide), wherein

• a) homofarnesylic acid of the formula Ia
• is converted into sclareolide of the formula IIa
• wherein homofarnesylic acid of the formula Ia is brought into contact with a squalene-hopene cyclase (SHC), which is capable of cyclizing a polyunsaturated carboxylic acid, in particular homofarnesylic acid;
• wherein the SHC is produced from the transgenic SHC-overexpressing strain E. coli LU 15568;
• b) sclareolide of the formula IIa from step a) is reduced chemically to ambroxidol, and
• c) ambroxidol from step b) is cyclized chemically to ambroxide;
• wherein the SHC is selected from among:
• a) a polypeptide with the amino acid sequence of SEQ ID NO:
• 2,
• b) proteins obtained by deletion, insertion, substitution, addition, inversion or a combination of proteins derived as per a), comprising a polypeptide with a sequence identity of at least 90%, to the amino acid sequence as per SEQ ID NO:
• 2;
• and
• c) proteins which catalyze the cyclization of homofarnesylic acid to sclareolide and comprise the amino acid sequence as per SEQ ID NO:
• 3, 4, 5, or 6, or with a sequence identity of at last 90% to the amino acid sequence of SEQ ID NO:
• 3, 4, 5, or 6.