Beer is the most popular alcoholicbeverage in the world, and hop female cone play a key role for the unique flavor and aroma of brewing beer. Essential oils, bitter acids, and prenylchalcones account for the major three categories of specialized metabolites that are highly accumulated in the glandular trichomes of female cones, while different combinations of these compounds dictate the bittering and finishing of beer. Among these hops-specific chemicals, xanthohumol (XN) and demethylxanthohumol (DMX), with multiple pharmaceutical applications, are good to human health. Although all structural enzymes in the XN pathway have been functionally identified, biochemical mechanisms underlying highly efficient production of XN have not been fully resolved.

Recently, researchers from WANG Guodong’s group in the Institute of Genetics and Developmental Biology (IGDB), Chinese Academy of Sciences (CAS), collaborated with Prof. Richard Dixon from University of North Texas, USA and Prof. Jing-Ke Weng from Massachusetts Institute of Technology, USA identified and characterized two non-catalytic chalcone isomerase-like proteins (CHIL) that facilitate high efficiency XN/DMX production in H. lupulus through enhancing the catalytic efficiency of structural enzymes and stabilizing synthetic intermediates.

In this study, researchers found that type IV CHIL proteins of representative land plants contain conserved function to bind with CHS and enhance its activity. Chemical binding assays and structural docking uncover a novel function of HlCHIL1 to bind DMX and naringenin chalcone (NC) to stabilize the ring-open configuration, which is important for the bioactivities of these chalconoids.

This study also provides a proof-of-concept for large-scale prenylchalone production using engineered yeasts. In near future, the industrial brewing yeast engineered for production of different hops-specific chemicals (called hopped yeast strains) will be generated and applied to make health-prompting beers.

The research results were published online in PNAS entitled “Noncatalytic chalcone isomerase-fold proteins in Humulus lupulus are auxiliary components in prenylated flavonoid biosynthesis”.

This work is supported by grants from the National Natural Science Foundation of China, and the State Key Laboratory of Plant Genomics of China.

Source: The Institute of Geneticsand Developmental Biology (IGDB)

Time: 2018.5.19