Luteolin Phosphate Derivatives Generated by Cultivating Bacillus subtilis var. Natto BCRC 80517 with Luteolin

Abstract

Luteolin (LUT), a plant-derived flavone, exhibits various bioactivities; however, the poor aqueous solubility hampers its applications. Here, we revealed bioconversion of LUT by Bacillus subtilis BCRC 80517, yielding three water-soluble phosphate conjugates. These derivatives were identified as luteolin 4′-O-phosphate (L4′P), luteolin 3′-O-phosphate (L3′P), and luteolin 7-O-phosphate (L7P) by LC-ESI-MS/MS and NMR. Besides, we found that Bacillus subtilis BCRC 80517 was able to convert different levels of LUT but showed a limited conversion rate. By observing bacterial morphology with transmission electron microscopy and confocal fluorescence microscopy, we found that LUT disrupted the bacterial membrane integrity, which explained the incomplete conversion. Additionally, we revealed a spontaneous intramolecular transesterification of L4′P to L3′P, the thermodynamically more stable form, under acidic conditions and proposed the possible mechanism involving a cyclic phosphate as the intermediate. This study provides insight into development of a potent structural modification strategy to enhance the solubility of LUT through biophosphorylation.

Synthesis of Mono- and Polyazole Hybrids Based on Polyfluoroflavones

“…Flavones based on a 2-phenylchromen-4-one backbone are important heteroaromatic scaffolds in organic chemistry due to their availability and significant synthetic and biological potential [ 1 , 2 , 3 , 4 , 5 ]. The uniqueness of this heterocyclic backbone is also due to the fact that its derivatives are widely represented in the plant world, which often determines their diverse biological action [ 6 , 7 , 8 , 9 , 10 , 11 ]. Isolation, identification, and chemical modification of flavones of plant origin is one of the rapidly developing areas in drug design [ 12 , 13 ].…”