How hops produce the alpha bitter acids that give beer its distinctive taste

Hops are an essential ingredient in beer brewing and an important economic crop. The female flowers of hops are covered in small glandular trichomes that synthesize and store a variety of specialized metabolites, which collectively determine the flavor and quality of beer. Terpenes provide the distinctive aroma, xanthohumol has powerful antioxidant properties that benefit human health, and alpha bitter acids give beer its distinctive bitterness.

Historically, these compounds also served as natural preservatives, extending the shelf life of beer long before the advent of modern brewing techniques. While the primary biosynthesis pathway of alpha-bitter acids has long been elucidated, the enzyme responsible for the final step, alpha-bitter acid synthase (α-BAS), has remained functionally uncertain for more than a decade, although several candidate genes have been identified.

To solve this long-standing mystery, a research team led by Professor Wang Guodong of the Institute of Genetics and Developmental Biology (IGDB) of the Chinese Academy of Sciences has developed a highly sensitive liquid chromatography-mass spectrometry (LC–MS) detection method capable of distinguishing between the two chiral forms of bitter alpha acids (6S and 6R). their analysis, published in Plant Communicationsrevealed that hop glandular trichomes mainly accumulate 6S alpha-bitter acid.

Further investigations revealed that the starting material, bitter α-deoxyacid, undergoes spontaneous oxidation when exposed to air, leading to the formation of a racemic mixture of the 6S and 6R types. This spontaneous chemical reaction has hampered efforts to confirm the true function of bitter alpha acid synthase. However, by overcoming this technical challenge, the researchers were able to create a yeast heterologous expression system and systematically test more than a dozen candidate genes.

The results identified HlMO18 as the enzyme that specifically catalyzes the oxidation of bitter α-deoxyacid to produce a predominantly 6S form. The researchers also identified key amino acid residues that are essential for enzyme activity. Additional mechanistic analyzes revealed that 6S-type alpha-bitter acid synthase forms a metabolic complex with upstream enzymes, which explains why the 6S form accumulates only in glandular trichomes.

This work complements the synthetic map of bitter alpha acids in hops and provides valuable insights for the brewing industry. Researchers have now elucidated the biosynthesis pathways for the three main flavor compounds in hops.

Looking to the future, they plan to use synthetic biology to engineer industrial yeast strains that could produce “hops beers,” which have the flavors of authentic hops but are not made with hop plants. This approach can reduce production costs and allow for more personalized, flavor-rich beers, providing a new direction for innovation in the brewing industry.