Microbial transformations of chalcones: hydroxylation, O-demethylation, and cyclization to flavanones.
Microorganisms were examined for their potential to catalyze biotransformation reactions that mimic plant biosynthetic processes. Specifically, microorganisms were screened for their abilities to transform selected chalcones to flavonoid and other products. Aspergillus alliaceus UI 315 efficiently transformed 3-(2' ',3' '-dimethoxyphenyl)-1-(2'-hydroxyphenyl)propenone (2'-hydroxy-2,3-dimethoxychalcone) (1) to several products, all of which were characterized by UV, NMR, and mass spectral analyses. A. alliaceus cyclized 1 to three flavanones and to O-demethylated and hydroxylated chalcones, some of which functioned as intermediates in the cyclization process. Inhibition studies using SKF525A, metyrapone, and phenylthiocarbamide with whole cell reactions showed that as many as three cytochrome P450 enzymes may be involved in these reactions. One enzyme catalyzed chalcone cyclization; another, O-demethylation; and a third, hydroxylation of chalcones. Flavonoid products are racemic, unlike the same products that are stereoselectively cyclized in plants. This work shows that microorganisms are capable of cyclizing chalcones to form flavonoid products, thus affording a mimic of plant biosynthetic processes.
Sanchez-Gonzalez
M
M
Division of Medicinal and Natural Products Chemistry, Center for Biocatalysis and Bioprocessing, College of Pharmacy, University of Iowa, Iowa City, Iowa 52242, USA.
Rosazza
J P N
JP
D001230:Aspergillus / Q000378:metabolism*; D001711:Biotransformation; D002384:Catalysis; D002599:Chalcone / Q000378:metabolism*; D003500:Cyclization; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D044950:Flavanones / Q000737:chemistry / Q000378:metabolism*; D006900:Hydroxylation; D007700:Kinetics; D008797:Metyrapone / Q000494:pharmacology; D018716:Molecular Mimicry; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010670:Phenylthiourea / Q000494:pharmacology; D011335:Proadifen / Q000494:pharmacology
D044950:Flavanones; D002599:Chalcone; D010670:Phenylthiourea; D003577:Cytochrome P-450 Enzyme System; D011335:Proadifen; D008797:Metyrapone