Two novel compounds (lovastatin analog Y and lovastatin analog Z) isolated from health foods containing beni-koji (red yeast rice) with adverse events report

Abstract

Ingestion of a contaminated health food product containing beni-koji (red yeast rice), one of the so-called “Foods with Functional Claims (FFC),’’ was recently reported to have adverse health effects, such as kidney damage. We previously revealed the presence of unexpected components, namely lovastatin analog Y and lovastatin analog Z, in contaminated FFC samples, which, incidentally, also contained puberulic acid. However, the structures and stereochemistries of these novel compounds remain unknown. In this study, we addressed this by conducting a comprehensive instrumental analysis of lovastatin analogs Y and Z isolated from the FFC samples. The two-dimensional structures of the isolated compounds were determined by ultra-high-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) and NMR spectroscopy. Their absolute configurations were established by comparison with those of chemically synthesized lovastatin analogs Y and Z. X-ray structural analysis using the crystalline sponge method confirmed that the synthesized lovastatin analogs Y and Z have the same absolute configuration as lovastatin acid. UHPLC-HRMS and NMR analyses further showed that the absolute configurations of lovastatin analogs Y and Z isolated from the FFC samples are identical to those of the synthesized compounds. Considering that lovastatin analogs Y and Z are produced through the co-incubation of Monascus pilosus and Penicillium adametzioides, these findings are expected to contribute to biosynthetic research related to these fungal species.

Graphical abstract