Structure-specific metabolism of flavonol molecules by Bacillus subtilis var. natto BCRC 80517

Abstract

Flavonols (3-hydroxy flavones) have been studied for their beneficial bioactivities for human health. Recently, we reported that a flavonoid phosphate synthetase (BsFPS) from Bacillus subtilis BCRC 80517 can transform several flavonoids into their phosphate conjugates, which become more water-soluble and thus increase the oral bioavailability. However, the in vivo metabolism of different flavonols has yet to be determined. Here, we investigated biotransformation of three flavonols (quercetin, kaempferol and fisetin) by B. subtilis BCRC 80517. C-ring cleavage products of quercetin and kaempferol, i.e., 2-protocatechuoyl-phloroglucinol carboxylic acid (2-PCPGCA), were produced, whereas two phosphate derivatives of fisetin (fisetin 4'-O-phosphate and fisetin 3'-O-phosphate) were generated by cultivation with B. subtilis BCRC 80517. Our results indicated that there are structure-specific metabolic pathways in B. subtilis toward different flavonols, where the 5-hydroxy group determines metabolic priority. Our findings provide new insights for developing bioproduction platform to produce flavonol phosphate derivatives for nutraceutical applications.

Keywords: 2-protocatechuoyl-phloroglucinol carboxylic acid (PubChem CID: 54675870); Bacillus subtilis; Biotransformation; C-ring cleavage; Flavonol; Phosphorylation; fisetin (PubChem CID: 5281614); kaempferol (PubChem CID: 5280863); kojic acid (PubChem CID: 3840); quercetin (PubChem CID: 5280343).