Efficient Reduction of Para-Cresol by Recombinant Saccharomyces cerevisiae through Regulated Expression of Heterologous 4-Methylphenyl Phosphate Synthase

para-Cresol is common in various fermented foods with an off-flavor odor. It is important to develop an efficient strategy for the reduction of p-cresol. Here, Clostridium fermenticellae JNCS001 (C. 001), which produces p-cresol, was isolated to explore the reduction strategy. The ability of C. 001 to produce p-cresol was assessed. The enzyme p-hydroxyphenylacetate decarboxylase (p-Hpd) and precursor tyrosine (Tyr) were identified as being responsible for p-cresol production. Following the introduction of the RgTAL gene from Rhodotorula glutinis into Saccharomyces cerevisiae CEN.PK 2-1C, only 21% of p-cresol produced by C. 001 was reduced through the competitive utilization of the precursor Tyr. To further enhance p-cresol reduction, 4-methylphenyl phosphate synthase CreIH from Corynebacterium glutamicum ATCC 13032 was introduced. By increasing the number of creIH genes, the recombinant yeast achieved a p-cresol reduction efficiency of 87% under aerobic conditions and 65% under anaerobic conditions. Finally, coculturing recombinant yeast with C. 001 under anaerobic conditions reduced p-cresol by 50%. These strategies have the potential to be applied for the efficient reduction of p-cresol.