# Metabolic engineering Saccharomyces cerevisiae for de novo biosynthesis of hydroxycinnamoyl glycerols

## TL;DR

Scientists engineered yeast to produce valuable hydroxycinnamoyl glycerols, which have applications in food, pharmaceuticals, and cosmetics.

## Contribution

A novel de novo biosynthetic pathway for hydroxycinnamoyl glycerols in Saccharomyces cerevisiae was constructed and optimized.

## Key findings

- An engineered S. cerevisiae strain produced 1-O-p-coumaroylglycerol at 8.49 ± 2.29 μg/L in shake-flask fermentation.
- Optimization of metabolic pathways enhanced precursor availability for hydroxycinnamoyl glycerol synthesis.
- The study provides a foundation for producing other hydroxycinnamoyl glycerols using similar strategies.

## Abstract

Hydroxycinnamoyl glycerols (HCGs) are a class of bioconjugates characterized by the esterification of hydroxycinnamic acids with glycerol. Owing to their diverse biological activities, HCGs are considered high-value materials with potential applications in the food, pharmaceutical, and cosmetics industries. In this study, a de novo biosynthetic pathway of HCGs was constructed by integrating a p-coumaric acid-producing module and a 4-coumarate:coenzyme A ligase - hydroxycinnamoyltransferase (4CL-HCT) module into the genome of Saccharomyces cerevisiae. Through optimization of the primary metabolic pathway, fine-tuning of the shikimate pathway, and strategic selection of integration sites, the upstream metabolic flux in the S. cerevisiae strain was engineering to enhance the availability of l-tyrosine and l-phenylalanine precursors, as well as acetyl-coenzyme A (acetyl-CoA) and adenosine triphosphate (ATP) supply. As a result, the final engineered S. cerevisiae strain produced 1-O-p-coumaroylglycerol (1-OPCG) at a titer of 8.49 ± 2.29 μg/L in shake-flask fermentation. The strategies employed in this study provide a robust foundation for the synthesis of other HCGs.

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