Biodegradation of l‑Homocysteine by Kluyveromyces marxianus YZC-01 Isolated from Healthy Human Feces

Hyperhomocysteinemia (HHcy), defined as elevated serum homocysteine levels (>15 μmol/L), is implicated in multiple metabolic disorders. This study reports the isolation of a novel yeast strain, Kluyveromyces marxianus YZC-01, from healthy human feces. In vitro assays demonstrated efficient l-homocysteine biodegradation by both K. marxianus YZC-01 cells and their cell-free extracts. Whole-genome sequencing revealed, for the first time in probiotic yeast, a complete l-homocysteine metabolic pathway in this strain, with key genes encoding cystathionine β-synthase, cystathionine γ-lyase, homocysteine S-methyltransferase, S-adenosylmethionine synthetase, and 5-methyltetrahydropteroyltriglutamate-homocysteine methyltransferase. These findings establish a foundation for targeted metabolic engineering to optimize l-homocysteine biodegradation in K. marxianus YZC-01. These results indicate that K. marxianus YZC-01 is a promising probiotic strain for developing functional foods or live biotherapeutic products for HHcy intervention.