Issue 20, 2023

Reprogramming the metabolism of oleaginous yeast for sustainably biosynthesizing the anticarcinogen precursor germacrene A

Abstract

Due to the diverse structures and broad functions of terpenes, microbial biosynthesis of these compounds has been favored as a sustainable alternative to phytoextraction and chemosynthesis. Here, systematic metabolic engineering strategies were explored in the oleaginous yeast Yarrowia lipolytica for hyperproducing sesquiterpene germacrene A which serves as an important intermediate of numerous anticarcinogens. By identifying the most efficient germacrene A synthase to date, reconstructing the endogenous mevalonate pathway and extending the cytosolic acetyl-CoA pool by regulating lipid metabolism, the resulting strain overproduced 2.794 g L−1 germacrene A in shake flasks, which represented a 38-fold improvement over the initial strain. The engineered strain was subsequently capable of producing 39 g L−1 germacrene A at a yield of 0.181 g g−1 glucose during optimized bioreactor fermentation, with this being the highest sesquiterpene production level reported to date for Y. lipolytica. These results demonstrate that reprogramming the metabolism of the host cell by systematic metabolic engineering plays an essential role in diverting its inherent metabolic fluxes for sesquiterpene biosynthesis and these approaches can be extensively applied for synthesizing natural terpenes.

Graphical abstract: Reprogramming the metabolism of oleaginous yeast for sustainably biosynthesizing the anticarcinogen precursor germacrene A

Supplementary files

Article information

Article type
Paper
Submitted
17 מאי 2023
Accepted
03 אוג 2023
First published
04 אוג 2023

Green Chem., 2023,25, 7988-7997

Reprogramming the metabolism of oleaginous yeast for sustainably biosynthesizing the anticarcinogen precursor germacrene A

Q. Liu, G. Zhang, L. Su, P. Liu, S. Jia, Q. Wang and Z. Dai, Green Chem., 2023, 25, 7988 DOI: 10.1039/D3GC01661G

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