Utilization of a styrene-derived pathway for 2-phenylethanol production in budding yeast

• Published in: Applied microbiology and biotechnology Vol. 105; no. 6; pp. 2333 - 2340
• Main Authors: Mo, Qiwen, Chen, Huiyu, Fan, Cong, Zhang, Danli, Liu, Lingrui, Fu, Bixia, Yuan, Jifeng
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.03.2021; Springer; Springer Nature B.V
• Subjects: Alcohol; Alcohol, Denatured; Biomedical and Life Sciences; Biotechnological Products and Process Engineering; Biotechnology; Brewer's yeast; Cell culture; Cellular signal transduction; Chemical properties; Cosmetics; Flasks; Flavor; Importation; Life Sciences; Microbial Genetics and Genomics; Microbiology; Permease; Phenylalanine; Phenylethyl Alcohol; Production processes; Saccharomyces cerevisiae; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae Proteins; Saccharomycetales; Styrene; Styrene oxide; Styrenes; Synthesis; Yeast; Yeasts; China; Styrene oxide isomerase; Ehrlich pathway; Synthetic biology; Natural 2-phenylethanol; Styrene-derived pathway
• ISSN: 0175-7598; 1432-0614
• DOI: 10.1007/s00253-021-11186-1

2-Phenylethanol (2-PE) is an important flavor ingredient and is widely applied in the fields of food, cosmetics, and pharmaceuticals. Despite that Saccharomyces cerevisiae has the ability to naturally synthesize 2-PE via the Ehrlich pathway, de novo synthesis of 2-PE in high titer still remains a huge challenge. In this study, a non-native styrene degradation pathway was introduced into S. cerevisiae , which represents the first time to demonstrate the functional expression of “styrene-derived” 2-PE synthesis in yeast. Using a host strain engineered with L-phenylalanine (L-Phe) overproduction, the heterologous 2-PE pathway coupled with endogenous Ehrlich pathway produced 233 mg/L 2-PE under shake flasks. Additionally, we further engineered the permease transporters to improve the intracellular L-Phe availability, and further improved the 2-PE titer to 680 mg/L. Taken together, our work represents one of the pioneering reports to explore “styrene-derived” pathway in S. cerevisiae . The synthetic yeast described here might be used as a platform for the future development of next-generation high-yielding 2-PE yeast strains. Key Points • A styrene-derived pathway was established in yeast for 2-phenylethanol productions; membrane-associated styrene oxide isomerase was functional in yeast. • Transporter engineering to improve the L-phenylalanine importation with enhanced 2-phenylethanol productions. Graphical abstract