The inhibition of melanogenesis by yeast extracts from cultivations of recombinant Pichia
pastoris catalyzing ortho-hydroxylation of flavonoids was investigated. The recombinant yeast harbored
a fusion gene composed of the CYP57B3 gene from Aspergillus oryzae and a cytochrome reductase
gene from Saccharomyces cerevisiae. Ten flavonoids belonging to flavones, flavonols,
flavanones, flavanols, and isoflavones were evaluated for biotransformation by the recombinant strain.
The results showed that five flavonoids, including the flavone apigenin, the flavanones naringenin and
liquiritigenin, and the isoflavones daidzein and genistein, could be biotransformed. The yeast extracts
from the five biotransformation fermentations were then evaluated for inhibitory activity on melanogenesis
in cultured mouse B16 melanoma cells. Three yeast extracts from biotransformation fermentation feeding with
daidzein, genistein, or apigenin showed inhibitory activity on melanogenesis in the B16 cells, while the extract from genistein
biotransformation exhibited the highest activity. The yeast extract from genistein biotransformation also showed
inhibitory activity on cellular tyrosinase activity in the B16 cells. The present study shows a CYP with multiple flavonoid
substrates for the first time and highlights the usage of yeast extracts from cultivations of the recombinant yeast catalyzing
flavonoids’ biotransformation in the development of skin-whitening agents.
Keywords: Apigenin, biotransformation, daidzein, genistein, naringenin, liquiritigenin, P450, Pichia pastoris.
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