De novo biosynthesis of the hops bioactive flavonoid xanthohumol in yeast


The flavonoid xanthohumol is an important flavor substance in the brewing industry that has a wide variety of bioactivities. However, its unstable structure is easily oxidized during the brewing process, resulting in its low content in beer. Moreover, its extraction and purification from plants requires laborious and expensive procedures, and hops cultivation is susceptible to environmental factors.

Recently, our group has proposed a microbial platform for the de novo biosynthesis of xanthohumol from glucose. It can efficiently synthesize flavonoids, such as the key xanthohumol precursor demethylxanthohumol (DMX) and xanthohumol, owing to balancing the three parallel biosynthetic pathways and enhancing the prenylation efficiency by rewiring the cellular metabolism of Saccharomyces cerevisiae.

This study was published in Nature Communications on Jan. 4.

Engineering the yeast Saccharomyces cerevisiae for biosynthesis of xanthohumol by optimizing the biosynthetic pathway and rewiring the cellular metabolism

The researchers systematically engineered the budding yeast S. cerevisiae for an 83-fold improvement in the demethylxanthohumol (DMX) production (4 mg/L) by balancing the three parallel biosynthetic pathways, prenyltransferase engineering, enhancing precursor supply, enzyme fusion, and peroxisomal engineering. Furthermore, expressing of the last methylation step produced 142 μg/L xanthohumol in shake flasks from glucose.

"Our work constructed a microbial cell factory for biosynthesis of xanthohumol and provided feasible approaches to optimize other complex biosynthetic pathways of natural products," said Prof. ZHOU. (Text by Shan Yang, Image by YongjinZhou)