Bioproduction of α-humulene in metabolically engineered Escherichia coli and application in zerumbone synthesis

authored by: Semra Alemdar, Jan C. König, Steffen Hartwig, Thore Frister, Thomas Scheper, Sascha Beutel
Abstract: Zerumbone is a sesquiterpene ketone with potent anti-cancerogenic activities, produced in several ginger species of the Zingiberaceae familiy. We have investigated the biotechnological production of α-humulene, a precursor of zerumbone. By implementing a heterologous mevalonate pathway in combination with the α-humulene synthase expression, we effectively synthesized α-humulene from glucose in Escherichia coli. In this study, we developed a practical and efficient in situ separation method for α-humulene by comparison of extractive and adsorptive strategies. By the in situ adsorption of the product to the hydrophobic resin Amberlite® XAD4 we were able to increase α-humulene yield by 2310% to 60.2 mg/L. Furthermore we present an easy applicable, short subsequent chemical process for the conversion of α-humulene to zerumbone by using transition metal catalysis. To reduce process steps, the chemical reaction was carried out in the same solvent as the eluting solvent that was used to elute α-humulene from the adsorbent resin. By allylic oxidation of α-humulene with manganese^II chloride as a catalyst and tert.-butylhydroperoxide as an oxidizing agent we were able to synthetize zerumbone with a selectivity of 51.6%. Product and byproducts of the oxidation reaction were identified by GC-MS.
Organisation(s): Institute of Technical Chemistry
Type: Article
Journal: Engineering in life sciences
Volume: 17
Pages: 900-907
No. of pages: 8
ISSN: 1618-0240
Publication date: 08.06.2017
Publication status: Published
Peer reviewed: Yes
ASJC Scopus subject areas: Biotechnology, Environmental Engineering, Bioengineering
Sustainable Development Goals: SDG 3 - Good Health and Well-being
Electronic version(s): https://doi.org/10.1002/elsc.201700043 (Access: Open)