J Agric Food Chem. 2026 Sep 15. doi: 10.1021/acs.jafc.5c08774. Online ahead of print.

ABSTRACT

The pharmacological activity of protopanaxadiol (PPD) can be enhanced by oxidative modification. Compared with chemical synthesis and biotransformation, synthetic biology offers a more efficient and eco-friendly approach for modifying PPD. In this study, we identified two oxidases from Mucor spinosus. MsSDR3 oxidizes C3-OH of both dammarenediol-II and PPD to a ketone, while MsCYP3 oxidizes C12-OH of PPD to a ketone and hydroxylates PPD at C7β, C15α, and C11β positions. Combining MsSDR3/MsCYP3 with the enzymes involved in ginsenoside biosynthesis, we achieved de novo biosynthesis of seven ginsenoside aglycone analogues in Saccharomyces cerevisiae. Pharmacological evaluation indicated that 12-oxo-15α-hydroxy-protopanaxadiol (p3) showed higher anticolon cancer activity, and 7β-hydroxy-protopanaxadiol (p6) exhibited not only higher anticolon, antigastric, antiliver, antilung, and antipancreatic cancer activities but also higher cardioprotective activity than PPD. Our work establishes a green and sustainable platform for producing active ginsenoside aglycone analogues, paving the way for the development of drugs and functional foods.

PMID:42742465 | DOI:10.1021/acs.jafc.5c08774