Metabolic reprogramming and computation-aided protein engineering for high-level de novo biosynthesis for 2-phenylethanol in Pichia pastoris Article Swipe
Lijing Sun
,
S. Liu
,
Renjie Sun
,
Jinshan Li
,
Aiqun Yu
,
Adison Wong
,
Liangcai Lin
,
Cuiying Zhang
·
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1016/j.synbio.2025.05.004
YOU?
·
· 2025
· Open Access
·
· DOI: https://doi.org/10.1016/j.synbio.2025.05.004
2-Phenylethanol (2-PE), an aromatic compound with a characteristic rose fragrance, is extensively used in the food and cosmetic industries as a flavoring and fragrance agent. Due to limitations in obtaining 2-PE from natural plant sources, microbial cell factories offer a promising alternative for sustainable biosynthesis. In this study, Pichia pastoris was engineered to efficiently synthesize 2-PE. Using computer-assisted predictions of interactions between the key phenylpyruvate decarboxylase KDC2 and its substrates or products, an optimal enzyme variant was rationally designed to boost 2-PE production. Additionally, the shikimic acid pathway was enhanced, and a dynamic regulation promoter was employed to reduce competition from alternative pathways. These strategies significantly increased metabolic flux toward 2-PE production, achieving a titer of 2.81 g/L and 45.8-fold improvement over the non-engineered strain. By integrating controlled carbon feeding and in situ extraction to alleviate acetic acid inhibition and product toxicity, the recombinant strain achieved a final 2-PE titer of 7.10 g/L and a yield of 0.14 g/g glucose, the highest reported microbial production to date. This study highlights the significant potential of P. pastoris as a versatile cell factory for the green biosynthesis of 2-PE and other natural products.
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- Type
- article
- Language
- en
- Landing Page
- https://doi.org/10.1016/j.synbio.2025.05.004
- OA Status
- gold
- Cited By
- 1
- References
- 72
- Related Works
- 10
- OpenAlex ID
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All OpenAlex metadata
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https://openalex.org/W4410385509Canonical identifier for this work in OpenAlex
- DOI
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https://doi.org/10.1016/j.synbio.2025.05.004Digital Object Identifier
- Title
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Metabolic reprogramming and computation-aided protein engineering for high-level de novo biosynthesis for 2-phenylethanol in Pichia pastorisWork title
- Type
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articleOpenAlex work type
- Language
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enPrimary language
- Publication year
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2025Year of publication
- Publication date
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2025-05-15Full publication date if available
- Authors
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Lijing Sun, S. Liu, Renjie Sun, Jinshan Li, Aiqun Yu, Adison Wong, Liangcai Lin, Cuiying ZhangList of authors in order
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https://doi.org/10.1016/j.synbio.2025.05.004Publisher landing page
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YesWhether a free full text is available
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goldOpen access status per OpenAlex
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https://doi.org/10.1016/j.synbio.2025.05.004Direct OA link when available
- Concepts
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Pichia pastoris, Reprogramming, Metabolic engineering, Pichia, Biosynthesis, Computation, Biology, Computational biology, Computer science, Genetics, Gene, Algorithm, Recombinant DNATop concepts (fields/topics) attached by OpenAlex
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1Total citation count in OpenAlex
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10Other works algorithmically related by OpenAlex
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