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De novo biosynthesis of β-Arbutin in Komagataella phaffii based on metabolic engineering strategies

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Title: De novo biosynthesis of β-Arbutin in Komagataella phaffii based on metabolic engineering strategies
Authors: Jiashuo Yang, Liu Yang, Fengguang Zhao, Chunting Ye, Shuangyan Han
Source: Microbial Cell Factories, Vol 23, Iss 1, Pp 1-14 (2024)
Publisher Information: BMC, 2024.
Publication Year: 2024
Collection: LCC:Microbiology
Subject Terms: K. phaffii, β-Arbutin, Shikimate pathway, Methanol, Metabolic strategies, Microbiology, QR1-502
Description: Abstract Background β-Arbutin, found in the leaves of bearberry, stands out as one of the globally acknowledged eco-friendly whitening additives in recent years. However, the natural abundance of β-Arbutin is low, and the cost-effectiveness of using chemical synthesis or plant extraction methods is low, which cannot meet the requirements. While modifying the β-Arbutin synthesis pathway of existing strains is a viable option, it is hindered by the limited synthesis capacity of these strains, which hinders further development and application. Results In this study, we established a biosynthetic pathway in Komagataella phaffii for β-Arbutin production with a titer of 1.58 g/L. Through diverse metabolic strategies, including fusion protein construction, enhancing shikimate pathway flux, and augmenting precursor supplies (PEP, E4P, and UDPG), we significantly increased β-Arbutin titer to 4.32 g/L. Further optimization of methanol concentration in shake flasks led to a titer of 6.32 g/L titer after 120 h of fermentation, representing a fourfold increase over the initial titer. In fed-batch fermentation, strain UA3-10 set a record with the highest production to date, reaching 128.6 g/L in a 5 L fermenter. Conclusions This is the highest yield in the fermentation tank level of using microbial cell factories for de novo synthesis of β-Arbutin. Applying combinatorial engineering strategies has significantly improved the β-Arbutin yield in K. phaffii and is a promising approach for synthesizing functional products using a microbial cell factory. This study not only advances low-cost fermentation-based production of β-Arbutin but also establishes K. phaffii as a promising chassis cell for synthesizing other aromatic amino acid metabolites. Graphical abstract
Document Type: article
File Description: electronic resource
Language: English
ISSN: 1475-2859
Relation: https://doaj.org/toc/1475-2859
DOI: 10.1186/s12934-024-02525-8
Access URL: https://doaj.org/article/9918e27c6c024062bfe24e731d5f3d05
Accession Number: edsdoj.9918e27c6c024062bfe24e731d5f3d05
Database: Directory of Open Access Journals
Description
Abstract:Abstract Background β-Arbutin, found in the leaves of bearberry, stands out as one of the globally acknowledged eco-friendly whitening additives in recent years. However, the natural abundance of β-Arbutin is low, and the cost-effectiveness of using chemical synthesis or plant extraction methods is low, which cannot meet the requirements. While modifying the β-Arbutin synthesis pathway of existing strains is a viable option, it is hindered by the limited synthesis capacity of these strains, which hinders further development and application. Results In this study, we established a biosynthetic pathway in Komagataella phaffii for β-Arbutin production with a titer of 1.58 g/L. Through diverse metabolic strategies, including fusion protein construction, enhancing shikimate pathway flux, and augmenting precursor supplies (PEP, E4P, and UDPG), we significantly increased β-Arbutin titer to 4.32 g/L. Further optimization of methanol concentration in shake flasks led to a titer of 6.32 g/L titer after 120 h of fermentation, representing a fourfold increase over the initial titer. In fed-batch fermentation, strain UA3-10 set a record with the highest production to date, reaching 128.6 g/L in a 5 L fermenter. Conclusions This is the highest yield in the fermentation tank level of using microbial cell factories for de novo synthesis of β-Arbutin. Applying combinatorial engineering strategies has significantly improved the β-Arbutin yield in K. phaffii and is a promising approach for synthesizing functional products using a microbial cell factory. This study not only advances low-cost fermentation-based production of β-Arbutin but also establishes K. phaffii as a promising chassis cell for synthesizing other aromatic amino acid metabolites. Graphical abstract
ISSN:14752859
DOI:10.1186/s12934-024-02525-8