Xanthohumol is a

natural product A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical s ...

found in the female

inflorescence In botany, an inflorescence is a group or cluster of flowers arranged on a plant's Plant stem, stem that is composed of a main branch or a system of branches. An inflorescence is categorized on the basis of the arrangement of flowers on a mai ...

s of ''

Humulus lupulus ''Humulus lupulus'', the common hop or hops, is a species of flowering plant in the hemp family, Cannabaceae. It is a perennial, herbaceous climbing plant which sends up new shoots in early spring and dies back to a cold-hardy rhizome in autumn. ...

'', also known as hops. This compound is also found in

beer Beer is an alcoholic beverage produced by the brewing and fermentation of starches from cereal grain—most commonly malted barley, although wheat, maize (corn), rice, and oats are also used. The grain is mashed to convert starch in the ...

and belongs to a class of compounds that contribute to the bitterness and flavor of hops. Xanthohumol is a prenylated

chalconoid Chalconoids ( Greek: χαλκός ''khalkós'', "copper", due to its color), also known as chalcones, are natural phenols In organic chemistry, phenols, sometimes called phenolics, are a class of chemical compounds consisting of one or more hy ...

, biosynthesized by a type III

polyketide synthase Polyketide synthases (PKSs) are a family of multi- domain enzymes or enzyme complexes that produce polyketides, a large class of secondary metabolites, in bacteria, fungi, plants, and a few animal lineages. The biosyntheses of polyketides share ...

(PKS) and subsequent modifying

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

Biosynthesis

Xanthohumol is a prenylated chalconoid derived from a plant type III PKS, and is synthesized in the glandular trichromes of hop cones.

L-Phenylalanine Phenylalanine (symbol Phe or F) is an essential α-amino acid with the formula . It can be viewed as a benzyl group substituted for the methyl group of alanine, or a phenyl group in place of a terminal hydrogen of alanine. This essential amin ...

serves as the starting material, which is converted to

cinnamic acid Cinnamic acid is an organic compound with the formula phenyl, C6H5-CH=CH-Carboxylic acid, COOH. It is a white crystalline compound that is slightly soluble in water, and freely soluble in many organic solvents. Classified as an unsaturated carboxy ...

by the PLP-dependent

phenylalanine ammonia lyase The enzyme phenylalanine ammonia lyase (EC 4.3.1.24) catalyzes the conversion of L-phenylalanine to ammonia and ''trans''-cinnamic acid.: :L-phenylalanine = ''trans''-cinnamate + NH3 Phenylalanine ammonia lyase (PAL) is the first and committe ...

. Cinnamic acid is oxidized by cinnamate-4-hydroxylase and loaded onto

coenzyme A Coenzyme A (CoA, SHCoA, CoASH) is a coenzyme, notable for its role in the Fatty acid metabolism#Synthesis, synthesis and Fatty acid metabolism#.CE.B2-Oxidation, oxidation of fatty acids, and the oxidation of pyruvic acid, pyruvate in the citric ac ...

(CoA) by 4-coumarate CoA ligase to yield 4-hydroxy-cinnamoyl CoA, the starter unit for PKS extension. This molecule is extended three times with

malonyl CoA Malonyl-CoA is a coenzyme A derivative of malonic acid. Biosynthesis Malonyl-CoA cannot cross membranes and there is no known malonyl-CoA import mechanism. The biosynthesis therefore takes place locally: * cytosol: Malonyl-CoA is formed by car ...

, cyclized through a

Claisen condensation The Claisen condensation is a carbon–carbon bond forming reaction that occurs between two esters or one ester and another carbonyl compound in the presence of a strong base. The reaction produces a β-keto ester or a β- diketone. It is named ...

, and aromatized through

tautomer In chemistry, tautomers () are structural isomers (constitutional isomers) of chemical compounds that readily interconvert. The chemical reaction interconverting the two is called tautomerization. This conversion commonly results from the reloca ...

ization to form

naringenin chalcone Naringenin chalcone is a common chalconoid (or chalcone, not to be confused with the compound chalcone). It is synthesized from 4-coumaroyl-CoA and malonyl-CoA by chalcone synthase (CHS), a key enzyme in the phenylpropanoid pathway. Naringenin c ...

(chalconaringenin). This intermediate has the potential to form a variety of different products depending on the enzymes that modify the core structure. In the case of xanthohumol, a

prenyltransferase Prenyltransferases (PTs) are a class of enzymes that transfer allylic prenyl groups to acceptor molecules. Prenyl transferases commonly refer to isoprenyl diphosphate syntheses (IPPSs). Prenyltransferases are a functional category and include seve ...

called ''Humulus lupulus'' prenyltransferase 1 (HlPT-1) attaches a molecule of

dimethylallyl pyrophosphate Dimethylallyl pyrophosphate (DMAPP; or alternatively, dimethylallyl diphosphate (DMADP); also isoprenyl pyrophosphate) is an isoprenoid precursor. It is a product of both the mevalonate pathway and the MEP pathway of isoprenoid precursor biosynt ...

from the DXP pathway. HlPT-1 has a broad substrate specificity and also participates in making other prenylated flavonoids in the hop plant. Finally, an

O-methyltransferase An O-methyltransferase (OMT) is a type of methyltransferase enzyme transferring a methyl group on a molecule. Examples are : * Acetylserotonin O-methyltransferase * Apigenin 4'-O-methyltransferase * Caffeate O-methyltransferase * Caffeoyl-CoA O-me ...

methylates a phenol substituent using

S-adenosyl methionine ''S''-Adenosyl methionine (SAM), also known under the commercial names of SAMe, SAM-e, or AdoMet, is a common cosubstrate involved in methyl group transfers, transsulfuration, and aminopropylation. Although these anabolic reactions occur thro ...

. Total syntheses of xanthohumol and derivatives have been achieved, though extraction from hops remains a primary source. Xanthohumol Biosynthesis v2

Beer

In commercial beers, the concentration of xanthohumol ranges from about 2 μg/L – 1.2 mg/L. During the

brewing Brewing is the production of beer by steeping a starch source (commonly cereal grains, the most popular of which is barley) in water and #Fermenting, fermenting the resulting sweet liquid with Yeast#Beer, yeast. It may be done in a brewery ...

process, xanthohumol and other prenylated flavonoids are lost as they are converted to the corresponding

flavanone The flavanones, a type of flavonoids, are various aromatic, colorless ketones derived from flavone that often occur in plants as glycosides. List of flavanones * Blumeatin * Butin * Dichamanetin * Eriodictyol * Hesperetin * Hesperidin * Hom ...

s. Different hop varieties and different beers contain varying quantities of xanthohumol.

Research

Xanthohumol is under

basic research Basic research, also called pure research, fundamental research, basic science, or pure science, is a type of scientific research with the aim of improving scientific theories for better understanding and prediction of natural or other phenome ...

for its potential biological properties. Xanthohumol can be extracted with pressurized hot water. Xanthohumol may have potential as a killer of bladder cancer.M.J. Bolt, J. Oceguera, A. Rivera Tostado, C.D. Candler, E. Mosa, K.Safari, M.G. Mancini, M.A. Mancini. A phenotypic screen identifies xanthohumol and other flavonoids as killers of bladder cancer. Pharmacological Research - Natural Products 2025 June vol 7, Pages 100236
See also

* Isoxanthohumol
, the corresponding prenylated flavanone * 8-Prenylnaringenin">Isoxanthohumol"> See also

* Isoxanthohumol
, the corresponding prenylated flavanone * 8-Prenylnaringenin, a related prenylflavanoid with estrogenic activity * Alpha acids, a class of bitter compounds in hops * Myrcene, humulene, and caryophyllene, essential oils in hops

References

{{reflist, 30em Chalconoids O-methylated natural phenols Humulus