Overexpression of a novel gene FCC1 enhances low-pH tolerance of the non-traditional yeast Pichia kudriavzevii.

Pichia kudriavzevii is a non-conventional yeast with significant potential for industrial applications, especially in organic acid fermentation, due to its remarkable tolerance to acidic conditions. In this study, we characterized the gene FCC1 in P. kudriavzevii and investigated its role in low-pH tolerance. FCC1 encodes a putative protein containing a Flo11 domain and two CBM1 domains. Gene disruption and overexpression studies demonstrated that FCC1 overexpression improved cell growth under low-pH conditions, while its deletion enhanced filamentous growth. Further analysis revealed that overexpression of FCC1 enhanced the yeast’s resistance to various weak organic acids, including acetic, lactic, citric, and malic acids. FCC1 overexpression may contribute to maintain cell membrane/wall integrity and intracellular pH homeostasis, and reduced oxidative stress. Transcriptomic analysis revealed that FCC1 overexpression modulated the expression of genes involved in cell wall remodeling, ion transport, and antioxidant defense, which are critical for yeast survival under low-pH conditions. Our findings highlight FCC1 as a potential target for genetic engineering to enhance the industrial use of P. kudriavzevii, particularly in applications that require robust acid stress tolerance, such as 2G bioethanol and organic acid production.