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Production of sesquiterpene patchoulol in mitochondrion-engineered Saccharomyces cerevisiae

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Abstract

Patchoulol is a natural sesquiterpene, which is widely used in perfumes and cosmetics. In the work, the mitochondria of S. cerevisiae were engineered for patchoulol production. The patchoulol titer of mitochondria-compartmentalized strain (1.79 mg/L) was 2.71-fold higher than that of control strain (0.66 mg/L) using genome-integrated patchoulol synthase, indicating that mitochondria compartmentation resulted in higher concentration of FPP (farnesyl pyrophosphate) precursor for patchoulol production. Moreover, when fused FPP synthase and patchoulol synthase was overexpressed in the strain with a mitochondria-localized DMAPP (dimethylallyl diphosphate) pathway, the production of patchoulol increased significantly to 19.24 mg/L, indicating more precursors were provided for patchoulol production. Nevertheless, the introduction of excess foreign proteins into mitochondria might cause a certain stress on mitochondria and showed a negative effect on the growth of yeast cells, which could hinder the expression of foreign pathways and reduce the patchoulol production. In conclusion, mitochondria-engineered yeast cells showed important potential for the enhanced biosynthesis of patchoulol, and further engineering could be considered based on the present work.

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Data availability

The datasets supporting the conclusions of this article are included in the main manuscript file.

Abbreviations

FPP:

Farnesyl pyrophosphate

DMAPP:

Dimethylallyl diphosphate

IPP:

Isopentenyl pyrophosphate

MEP:

2-C-methyl-derythritol 4-phosphate

MVA:

Mevalonic acid

GPP:

Geranyl pyrophosphate

GGPP:

Geranylgeranyl pyrophosphate

GC:

Gas chromatography

FID:

Flame ionization detector

PT:

Patchoulol synthase

FPT:

Fused FPP synthase and patchoulol synthase

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Acknowledgements

This study was supported by National Key Research and Development Program of China (2021YFC2100300), the National Natural Science Foundation of China (No. 31500043), the Natural Science Foundation of Shanghai (No. 21ZR1417200), and the Open Funding Project of the State Key Laboratory of Bioreactor Engineering.

Funding

Funding was provided by National Natural Science Foundation of China (Grant Number 31500043) Natural Science Foundation of Shanghai (Grant Number 21ZR1417200), National Key Research and Development Program of China (Grant Number 2021YFC2100300) and Open Funding Project of the State Key Laboratory of Bioreactor Engineering.

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Authors and Affiliations

  1. State Key Lab of Bioreactor Engineering, Newworld Institute of Biotechnology, East China University of Science and Technology, Shanghai, 200237, China

    Xin-Yi Tao, Yang-Chen Lin, Feng-Qing Wang, Qing-Hai Liu, Yu-Shu Ma, Min Liu & Dong-Zhi Wei

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  1. Xin-Yi Tao
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  2. Yang-Chen Lin
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  6. Min Liu
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Correspondence to Yu-Shu Ma or Min Liu.

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Tao, XY., Lin, YC., Wang, FQ. et al. Production of sesquiterpene patchoulol in mitochondrion-engineered Saccharomyces cerevisiae. Biotechnol Lett 44, 571–580 (2022). https://doi.org/10.1007/s10529-022-03240-3

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  • DOI: https://doi.org/10.1007/s10529-022-03240-3

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