Promoter engineering enables precise metabolic regulation towards efficient β-elemene production in Ogataea polymorpha

Ye, Min; Gao, Jiaoqi; Li, Jingjing; Yu, Wei; Bai, Fan; Zhou, Yongjin J.

doi:10.1016/j.synbio.2024.02.001

Synthetic and Systems Biotechnology

2024

DOI: 10.1016/j.synbio.2024.02.001

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Promoter engineering enables precise metabolic regulation towards efficient β-elemene production in Ogataea polymorpha

Min Ye,

Jiaoqi Gao,

Jingjing Li

et al.

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2024

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Cited by 6 publications

References 65 publications

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Engineering a versatile yeast platform for sesquiterpene production from glucose or methanol

Gao,

Zhang,

Shen

et al. 2024

Biotechnology Journal

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Natural sesquiterpene are valuable compounds with diverse applications in industries, such as cosmetics and energy. Microbial synthesis offers a promising way for sesquiterpene production. Methanol, can be synthesized from CO2 and solar energy, serves as a sustainable carbon source. However, it is still a challenge to utilize methanol for the synthesis of value‐added compounds. Pichia pastoris (syn. Komagataella phaffii), known for its efficient utilization of glucose and methanol, has been widely used in protein synthesis. With advancements in technology, P. pastoris is gradually engineered for chemicals production. Here, we successfully achieved the synthesis of α‐bisabolene in P. pastoris with dual carbon sources by expressing the α‐bisabolene synthase gene under constitutive promoters. We systematically analyzed the effects of different steps in the mevalonate (MVA) pathway when methanol or glucose was used as the carbon source. Our finding revealed that the sesquiterpene synthase module significantly increased the production when methanol was used. While the metabolic modules MK and PMK greatly improved carbon source utilization, cell growth, and titer when glucose was used. Additionally, we demonstrated the synthesis of β‐farnesene from dual carbon source by replacing the α‐bisabolene synthase with a β‐farnesene synthase. This study establishes a platform strain that is capable to synthesize sesquiterpene from different carbon sources in P. pastoris. Moreover, it paves the way for the development of P. pastoris as a high‐efficiency microbial cell factory for producing various chemicals, and lays foundation for large‐scale synthesis of high value‐added chemicals efficiently from methanol in P. pastoris.

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Engineering a versatile yeast platform for sesquiterpene production from glucose or methanol

Gao,

Zhang,

Shen

et al. 2024

Biotechnology Journal

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Screening and modification of (+)-germacrene A synthase for the production of the anti-tumor drug (−)-β-elemene in engineered Saccharomyces cerevisiae

Hu,

Zhang,

Bai

et al. 2024

International Journal of Biological Macromolecules

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Ogataea polymorpha as a next-generation chassis for industrial biotechnology

Xie,

Yu,

Gao

et al. 2024

Trends in Biotechnology

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Promoter engineering enables precise metabolic regulation towards efficient β-elemene production in Ogataea polymorpha

Cited by 6 publications

References 65 publications

Engineering a versatile yeast platform for sesquiterpene production from glucose or methanol

Engineering a versatile yeast platform for sesquiterpene production from glucose or methanol

Screening and modification of (+)-germacrene A synthase for the production of the anti-tumor drug (−)-β-elemene in engineered Saccharomyces cerevisiae

Ogataea polymorpha as a next-generation chassis for industrial biotechnology

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