Metabolic engineering of Saccharomyces cerevisiae for production of germacrene A, a precursor of beta-elemene
Artikel i vetenskaplig tidskrift, 2017

Beta-elemene, a sesquiterpene and the major component of the medicinal herb Curcuma wenyujin, has antitumor activity against various types of cancer and could potentially serve as a potent antineoplastic drug. However, its current mode of production through extraction from plants has been inefficient and suffers from limited natural resources. Here, we engineered a yeast cell factory for the sustainable production of germacrene A, which can be transformed to beta-elemene by a one-step chemical reaction in vitro. Two heterologous germacrene A synthases (GASs) converting farnesyl pyrophosphate (FPP) to germacrene A were evaluated in yeast for their ability to produce germacrene A. Thereafter, several metabolic engineering strategies were used to improve the production level. Overexpression of truncated 3-hydroxyl-3-methylglutaryl-CoA reductase and fusion of FPP synthase with GAS, led to a sixfold increase in germacrene A production in shake-flask culture. Finally, 190.7 mg/l of germacrene A was achieved. The results reported in this study represent the highest titer of germacrene A reported to date. These results provide a basis for creating an efficient route for further industrial application re-placing the traditional extraction of beta-elemene from plant sources.

Germacrene A

Metabolic engineering

Beta-elemene

Saccharomyces cerevisiae

Författare

Yating Hu

Chalmers, Biologi och bioteknik, Systembiologi

Yongjin Zhou

Chalmers, Biologi och bioteknik, Systembiologi

Jichen Bao

Chalmers, Biologi och bioteknik, Systembiologi

L. Q. Huang

China Academy of Chinese Medical Sciences

Jens B Nielsen

Chalmers, Biologi och bioteknik, Systembiologi

Anastasia Krivoruchko

Chalmers, Biologi och bioteknik, Systembiologi

Journal of Industrial Microbiology and Biotechnology

1367-5435 (ISSN) 1476-5535 (eISSN)

Vol. 44 7 1065-1072

Ämneskategorier

Industriell bioteknik

Bioinformatik och systembiologi

DOI

10.1007/s10295-017-1934-z