Metabolic engineering of Saccharomyces cerevisiae for high-level production of gastrodin from glucose

Abstract

Background The natural phenolic glycoside gastrodin is the major bioactive ingredient in the well-known Chinese herb Tianma and is widely used as a neuroprotective medicine in the clinic. Microbial production from sustainable resources is a promising method to replace plant extraction and chemical synthesis which were currently used in industrial gastrodin production. Saccharomyces cerevisiae is considered as an attractive host to produce natural plant products used in the food and pharmaceutical fields. In this work, we intended to explore the potential of S. cerevisiae as the host for high-level production of gastrodin from glucose. Results Here, we first identified the plant-derived glucosyltransferase AsUGT to convert 4-hydroxybenzyl alcohol to gastrodin with high catalytic efficiency in yeast. Then, we engineered de novo production of gastrodin by overexpressing codon-optimized AsUGTsyn, the carboxylic acid reductase gene CARsyn from Nocardia species, the phosphopantetheinyl transferase gene PPTcg-1syn from Corynebacterium glutamicum, the chorismate pyruvate-lyase gene UbiCsyn from Escherichia coli, and the mutant ARO4K229L. Finally, we achieved an improved product titer by a chromosomal multiple-copy integration strategy and enhancement of metabolic flux toward the aglycon 4-hydroxybenzyl alcohol. The best optimized strain produced 2.1 g/L gastrodin in mineral medium with glucose as the sole carbon source by flask fermentation, which was 175 times higher than that of the original gastrodin-producing strain. Conclusions The de novo high-level production of gastrodin was first achieved. Instead of chemical synthesis or plants extraction, our work provides an alternative strategy for the industrial production of gastrodin by microbial fermentation from a sustainable resource.

Correction to: Metabolic engineering of Saccharomyces cerevisiae for high-level production of gastrodin from glucose

“…Following publication of the original article [ 1 ], the authors identified an error in acknowledgement section. The correct acknowledgement is given below.…”

“…Author details 1 Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China. 2 Key Laboratory of Systems Microbial Biotechnology, Chinese Academy of Sciences, Tianjin 300308, China.…”

Metabolic Engineering of Escherichia coli for High-Level Production of Salicin

“… 14 , 15 A few important phenolic glycosides have been successfully synthesized in microorganisms by designing artificial pathways. 16 , 17 In the case of salicin production, microbial synthesis would offer an alternative route in addition to direct extraction from plants.…”

“… 26 In recent years, carboxylic acid reductases have demonstrated significant potential to reduce aromatic acids to produce aromatic aldehydes and aromatic alcohols in microorganisms. 17 , 20 , 27 , 28 The synthesis of salicylic alcohol in E. coli was further achieved by introducing a carboxylic acid reductase [carboxylate reductase (CAR) from Mycobacterium marinum ( M. marinum )]. 20 The biosynthetic pathway of salicylic acid from chorismate catalyzed by a salicylate synthase was also known in the biosynthesis of yersiniabactin oramychelin.…”

Whole-Cell Biocatalyst for Rubusoside Production in Saccharomyces cerevisiae

“…Therefore, great efforts have been made to regenerate UDPG in situ , aiming reduction of the UDPG supply cost in the microbial host. Recent research indicated that Saccharomyces cerevisiae (baker’s yeast), a Generally Regarded As Safe (GRAS) organism, might be a promising whole-cell biocatalyst host advantageous for the production of valuable glycosides including dietary supplements and pharmaceuticals. − S. cerevisiae holds a cytoplasmic pool of UDP glucose (UDPG) generated by the endogenous biosynthetic pathway involving phosphoglucomutase 1 (PGM1), phosphoglucomutase 2 (PGM2), and UDP-glucose pyrophosphorylase 1 (UGP1) (Figure B) .…”