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 syn ...

found in the female

inflorescence An inflorescence is a group or cluster of flowers arranged on a stem that is composed of a main branch or a complicated arrangement of branches. Morphologically, it is the modified part of the shoot of seed plants where flowers are formed o ...

s of ''

Humulus lupulus ''Humulus lupulus'', the common hop or hops, is a species of flowering plant in the hemp family Cannabinaceae, native to Europe, western Asia and North America. It is a perennial, herbaceous climbing plant which sends up new shoots in early spr ...

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

beer Beer is one of the oldest and the most widely consumed type of alcoholic drink in the world, and the third most popular drink overall after water and tea. It is produced by the brewing and fermentation of starches, mainly derived from ce ...

and belongs to a class of compounds that contribute to the bitterness and flavor of hops. Xanthohumol is a prenylated chalconoid, biosynthesized by a type III

polyketide synthase Polyketides are a class of natural products derived from a precursor molecule consisting of a chain of alternating ketone (or reduced forms of a ketone) and methylene groups: (-CO-CH2-). First studied in the early 20th century, discovery, biosynth ...

(PKS) and subsequent modifying

enzyme Enzymes () are proteins that act as biological catalysts by accelerating chemical reactions. The molecules upon which enzymes may act are called substrates, and the enzyme converts the substrates into different molecules known as products. A ...

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 amino ac ...

serves as the starting material, which is converted to

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

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 committed ...

. 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 synthesis and oxidation of fatty acids, and the oxidation of pyruvate in the citric acid cycle. All genomes sequenced to date encode enzymes that use coenzyme A as a subs ...

(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. Functions It plays a key role in chain elongation in fatty acid biosynthesis and polyketide biosynthesis. Fatty acid biosynthesis Malonyl-CoA provides 2-carbon units to fatty acids and commi ...

, 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, resulting in a β-keto ester or a β-diketone. It is named after Ra ...

, and aromatized through

tautomer 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 relocation of a hydr ...

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 ...

(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 ...

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 throug ...

. 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 * Eriodictyol * Hesperetin * Hesperidin * Homoeriodictyol * Iso ...

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

Research

Xanthohumol is under

basic research Basic research, also called pure research or fundamental research, is a type of scientific research with the aim of improving scientific theories for better understanding and prediction of natural or other phenomena. In contrast, applied resear ...

for its potential biological properties. Xanthohumol can be extracted with pressurized hot water.A. Gil-Ramírez, J.A. Mendiola, E. Arranz, A. Ruíz-Rodríguez, G. Reglero, E. Ibáñez, F.R. Marín
Highly isoxanthohumol enriched hop extract obtained by pressurized hot water extraction (PHWE). Chemical and functional characterization
Innovative Food Science and Emerging Technologies 2012 October, vol 16 Pages 54-60
doi: 10.1016/j.ifset.2012.04.006

References

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

Biosynthesis

Beer

Research

See also

References