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Metabolic engineering of Saccharomyces cerevisiae for co-production of ergothioneine, salidroside and gadusol.

Created on 19 Jun 2026

Authors

Leyi Zhang, Sen Xiao, Daoan Wang, Ping Zhang, Ruirui Xu, Litao Hu, Zhen Kang

Published in

Synthetic and systems biotechnology. Volume 14. Pages 471-479. Epub Jun 10, 2026.

Abstract

Ergothioneine (EGT), salidroside and gadusol are high-value cosmetic ingredients valued for their moisturizing, skin-brightening and ultraviolet (UV)-protective properties. Leveraging Saccharomyces cerevisia, a GRAS organism already widely used in cosmetics, we engineered a single strain for their simultaneous co-production. We first identified the 5-histidylcysteine sulfoxide synthase domain reaction as rate-limiting and addressed the poor solubility of ergothioneine biosynthesis protein 1 (EGT1) by screening heterologous homologs and optimizing EGT1 through solubility-enhancing fusions and structure-guided stabilization, increasing EGT titer in shake flask from 34 to 132 mg L-1. Multicopy integration of the optimized pathway into the ribosomal DNA (rDNA) locus further boosted EGT production to 690 mg L-1 in a 5-L bioreactor. Subsequently, biosynthetic pathways for salidroside and gadusol were introduced, yielding a tri-product strain that achieved final titers of 1329 mg L-1 EGT, 224 mg L-1 salidroside and 556 mg L-1 gadusol in fed-batch fermentation. This work establishes a multifunctional yeast cell factory capable of simultaneous co-production of multiple premium cosmetic actives, offering a scalable and sustainable platform for next-generation ingredient development.

PMID:
42318496
Bibliographic data and abstract were imported from PubMed on 19 Jun 2026.

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