The biotransformation of xanthohumol (1), a prenylated chalcone isolated from hops by selected fungi, was investigated. Microbial regioselective glycosylation at the C-4' position led to xanthohumol 4'-O-β-D-glucopyranoside (2) and xanthohumol 4'-O-β-D-(4'''-O-methyl)-glucopyranoside (3). The subsequent cyclization of 2 resulted in isoxanthohumol 7-O-β-glucopyranoside (4). The structures of the products were identified based on spectroscopic methods. The biological activity of isolated metabolites has been evaluated. Compared to xanthohumol (1), metabolite 2 is a better 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical scavenger, while 2 and 3 have stronger antiproliferative activity against the human HT-29 colon cancer cell line.

glycosylation, Antioxidant activity, Antiproliferative activity, biotransformation, xanthohumol, spent hops

There is only one chemically distinct structure:

SVGMWSMILES3D molIonize

 

COc1cc(O)c(CC=C(C)C)c(O)c1C(=O)/C=C/c1ccc(O[C@@H]2O[C@H](CO)[C@@H](OC)[C@H](O)[C@H]2O)cc1

530.57 g/mol (C₂₈H₃₄O₁₀)

A screening test on 29 microorganisms for transformation of xanthohumol led to the selection of twelve fungal strains. One of them, Beauveria bassiana AM278, converted xanthohumol into a glucosylated derivative. This product was identified as xanthohumol 4'-O-beta-D-4'''-methoxyglucopyranoside.

biotransformation, Beauveria bassiana, xanthohumol

13C NMR data:
Linkage	Residue	C1	C2	C3	C4	C5	C6	C7	C8	C9	C10	C11	C12	C13	C14	C15	C16	C17	C18	C19	C20	C21
4',4	Me	60.2
4'	bDGlcp	100.2	74.0	77.1	76.5	79.8	60.9
	Subst	126.4	131.2	116.5	160.6	116.5	131.2	143.8	124.1	193.2	106.7	163.6	110.0	161.5	91.0	160.9	56.5	21.7	123.2	130.6	18.2	26.0


1H NMR data:
Linkage	Residue	H1	H2	H3	H4	H5	H6	H7	H8	H9	H10	H11	H12	H13	H14	H15	H16	H17	H18	H19	H20	H21
4',4	Me	3.47
4'	bDGlcp	5.04	5.44	5.32	3.52	3.0	3.49-3.51
	Subst	-	7.61	6.86	-	6.86	7.61	7.72	7.76	-	-	-	-	-	6.39	-	3.93	3.35	5.19	-	1.74	1.61


1H/13C HSQC data:
Linkage	Residue	C1/H1	C2/H2	C3/H3	C4/H4	C5/H5	C6/H6	C7/H7	C8/H8	C9/H9	C10/H10	C11/H11	C12/H12	C13/H13	C14/H14	C15/H15	C16/H16	C17/H17	C18/H18	C19/H19	C20/H20	C21/H21
4',4	Me	60.2/3.47
4'	bDGlcp	100.2/5.04	74.0/5.44	77.1/5.32	76.5/3.52	79.8/3.0	60.9/3.49-3.51
	Subst		131.2/7.61	116.5/6.86		116.5/6.86	131.2/7.61	143.8/7.72	124.1/7.76						91.0/6.39		56.5/3.93	21.7/3.35	123.2/5.19		18.2/1.74	26.0/1.61

There is only one chemically distinct structure:

SVGMWSMILES3D molIonize

 

COc1cc(O)c(CC=C(C)C)c(O)c1C(=O)/C=C/c1ccc(O[C@@H]2O[C@H](CO)[C@@H](OC)[C@H](O)[C@H]2O)cc1

530.57 g/mol (C₂₈H₃₄O₁₀)

Flavonoids constitute a large group of polyphenolic compounds naturally found in plants, which have a wide range of biological activity. Although flavonoids are beneficial to human health, their application is limited by their low bioavailability and poor water-solubility. Therefore, recently there has been a particular interest in glycosylated forms of flavonoids, which usually are better soluble, more stable, and more functional compared to their aglycones. Microbial transformation of natural flavonoids may be an attractive way of receiving their glycosylated derivatives in amounts sufficient for the research on the effect of glycoside group on compound properties and for further application of these compounds as ingredients of dietary supplements and pharmaceuticals.

glycosides, biotransformation, microbial glycosylation, flavonoids

There is only one chemically distinct structure:

SVGMWSMILES3D molIonize

 

COc1cc(O)c(CC=C(C)C)c(O)c1C(=O)/C=C/c1ccc(O[C@@H]2O[C@H](CO)[C@@H](OC)[C@H](O)[C@H]2O)cc1

530.57 g/mol (C₂₈H₃₄O₁₀)