TY - JOUR

T1 - Bioproduction of α-humulene in metabolically engineered Escherichia coli and application in zerumbone synthesis

AU - Alemdar, Semra

AU - König, Jan C.

AU - Hartwig, Steffen

AU - Frister, Thore

AU - Scheper, Thomas

AU - Beutel, Sascha

N1 - Funding information: This study was funded by the European Regional Development Fund (EFRE): Innovation Network “Refinement of plant resources” (ZW-8-80130940). Special thanks to Daniel Sandner and Dr. Ulrich Krings (both Institute of Food Chemistry, Leibniz University Hannover) for performing GS-MS measurements. Jana Schellen-berg is gratefully acknowledged for assistance in the laboratory work.

PY - 2017/6/8

Y1 - 2017/6/8

N2 - 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 manganeseII 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.

AB - 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 manganeseII 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.

KW - Allylic oxidation

KW - In situ product recovery

KW - Integrated bioprocess

KW - Semi-synthesis

KW - Zerumbone

UR - http://www.scopus.com/inward/record.url?scp=85028358223&partnerID=8YFLogxK

U2 - 10.1002/elsc.201700043

DO - 10.1002/elsc.201700043

M3 - Article

AN - SCOPUS:85028358223

VL - 17

SP - 900

EP - 907

JO - Engineering in life sciences

JF - Engineering in life sciences

SN - 1618-0240

IS - 8

ER -