De novo biosynthesis of vanillin in engineered Saccharomyces cerevisiae. (14th December 2022)

• Record Type: Journal Article
• Authors: Qiu, Di; Wang, Minghai; Zhou, Chao; Zhao, Jinyu; Zhang, Genlin
• Is Part Of: Chemical engineering science. Volume 263(2022)
• Publication Date: 2022-12-14
• Subjects: Vanillin -- Pathway design -- Metabolic engineering -- Fermentation optimization -- Saccharomyces cerevisiae; Chemical engineering -- Periodicals; Génie chimique -- Périodiques; Chemical engineering; Periodicals; Electronic journals; 660
• DOI: 10.1016/j.ces.2022.118049
• Languages: English
• ISSNs: 0009-2509

Abstract

Highlights: De novo biosynthesis of vanillin in S. cerevisiae . Validation of caffeate O-methyltransferase as a rate-limiting enzyme for de novo biosynthesis of vanillin. Optimizing tyrosine supply significantly improved the titer of vanillin. Abstract: Vanillin, an important aldehyde compound, is widely used in food and medicine industries. Natural and chemical-synthesized vanillin are facing significant challenge for the sustainable development. Here, de novo biosynthesis of vanillin in S. cerevisiae was thus designed. Through integrating sam8, CYP199A2, comt, fcs and ech into the genome of S. cerevisiae, vanillin was successfully biosynthesized with a titer of 26.3 μg/L. Preferred sam5 efficiently enriched caffeic acid pool, improving vanillin production to 50.2 μg/L in haploid engineered yeast. Expressing the mutants of ARO4 K229L and ARO7 G141S had reduced the negative feedback of tyrosine, increased the vanillin titer to 700 μg/L. Finally, the titer of vanillin was increased to 8545 μg/L through supplying 400 mg/L ferulic acid. The strategies of metabolic engineering and fermentation optimization achieved de novo biosynthesis of vanillin in S. cerevisiae, showing the feasibility of vanillin production by microbial technology.