Although constituting a limited chemical family, phytostilbenes represent an emblematic group of molecules among natural compounds.

Salidroside is an important plant-derived aromatic compound with diverse biological properties. Because of inadequate natural resources, the supply of salidroside is currently limited. In this work, we engineered the production of salidroside in yeast. First, the aromatic aldehyde synthase (AAS) from Petroselinum crispum was overexpressed in Saccharomyces cerevisiae when combined with endogenous Ehrlich pathway to produce tyrosol from tyrosine. Glucosyltransferases from different resources were tested for ideal production of salidroside in the yeast. Metabolic flux was enhanced toward tyrosine biosynthesis by overexpressing pathway genes and eliminating feedback inhibition. The pathway genes were integrated into yeast chromosome, leading to a recombinant strain that produced 239.5 mg/L salidroside and 965.4 mg/L tyrosol. The production of salidroside and tyrosol reached up to 732.5 and 1394.6 mg/L, respectively, by fed-batch fermentation. Our work provides an alternative way for industrial large-scale production of salidroside and tyrosol from S. cerevisiae.

This work not only leads to high yield production of rosmarinic acid and analogues, but also sheds new light on the construction of the pathway of rosmarinic acid in E. coli.

This work demonstrates the viability of synthesizing a broad range of rosmarinic acid analogues in E. coli, and sheds new light on the substrate specificity of CbRAS.

Three rosmarinic acid analogs produced by recombinant Escherichia coli, two xanthones from fungi and honokiol from plants, were explored as the substrates of E. coli harboring a glucosyltransferase mutant UGT73B6 to generate phenolic glucosides. Six new and two known compounds were isolated from the fermentation broth of the recombinant strain of the feeding experiments, and the compounds were identified by spectroscopy. The biotransformation of rosmarinic acid analogs and xanthones into corresponding glucosides was presented for the first time. This study not only demonstrated the substrate flexibility of the glucosyltransferase mutant UGT73B6 toward aromatic alcohols but also provided an effective and economical method to produce phenolic glucosides by fermentation circumventing the use of expensive precursor UDP-glucose.

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