A tailored series of engineered yeasts for the cell-dependent treatment of inflammatory bowel disease by rational butyrate supplementation.

Intestinal microbiota dysbiosis and metabolic disruption are considered essential characteristics in inflammatory bowel disorders (IBD). Reasonable butyrate supplementation can help patients regulate intestinal flora structure and promote mucosal repair. Here, to restore microbiota homeostasis and butyrate levels in the patient's intestines, we modified the genome of Saccharomyces cerevisiae to produce butyrate. We precisely regulated the relevant metabolic pathways to enable the yeast to produce sufficient butyrate in the intestine with uneven oxygen distribution. A series of engineered strains with different butyrate synthesis abilities was constructed to meet the needs of different patients, and the strongest can reach 1.8 g/L title of butyrate. Next, this series of strains was used to co-cultivate with gut microbiota collected from patients with mild-to-moderate ulcerative colitis. After receiving treatment with engineered strains, the gut microbiota and the butyrate content have been regulated to varying degrees depending on the synthetic ability of the strain. The abundance of probiotics such as Bifidobacterium and Lactobacillus increased, while the abundance of harmful bacteria like Candidatus Bacilloplasma decreased. Meanwhile, the series of butyrate-producing yeast significantly improved trinitrobenzene sulfonic acid (TNBS)-induced colitis in mice by restoring butyrate content. Among the series of engineered yeasts, the strain with the second-highest butyrate synthesis ability showed the most significant regulatory and the best therapeutic effect on the gut microbiota from IBD patients and the colitis mouse model. This study confirmed the existence of a therapeutic window for IBD treatment by supplementing butyrate, and it is necessary to restore butyrate levels according to the actual situation of patients to restore intestinal flora.

Biological valorization of lignin to flavonoids.

Lignin is the most affluent natural aromatic biopolymer on the earth, which is the promising renewable source for valuable products to promote the sustainability of biorefinery. Flavonoids are a class of plant polyphenolic secondary metabolites containing the benzene ring structure with various biological activities, which are largely applied in health food, pharmaceutical, and medical fields. Due to the aromatic similarity, microbial conversion of lignin derived aromatics to flavonoids could facilitate flavonoid biosynthesis and promote the lignin valorization. This review thereby prospects a novel valorization route of lignin to high-value natural products and demonstrates the potential advantages of microbial bioconversion of lignin to flavonoids. The biodegradation of lignin polymers is summarized to identify aromatic monomers as momentous precursors for flavonoid synthesis. The biosynthesis pathways of flavonoids in both plants and strains are introduced and compared. After that, the key branch points and important intermediates are clearly discussed in the biosynthesis pathways of flavonoids. Moreover, the most significant enzyme reactions including Claisen condensation, cyclization and hydroxylation are demonstrated in the biosynthesis pathways of flavonoids. Finally, current challenges and potential future strategies are also discussed for transforming lignin into various flavonoids. The holistic microbial conversion routes of lignin to flavonoids could make a sustainable production of flavonoids and improve the feasibility of lignin valorization.