Background: Two important flavonoids, kaempferol and quercetin possess remarkably potent biological impacts on human health. However, their structural complexity and low abundance in nature make both bulk chemical synthesis and extraction from native plants difficult. Therefore microbial production via heterologous expression of plant enzymes can be a safe and sustainable route for their production. Despite several attempts reported in microbial hosts, the production levels of kaempferol and quercetin still stay far behind compared to many other microbial-produced flavonoids. Results: In this study, Saccharomyces cerevisiae was engineered for high production of kaempferol and quercetin in minimal media from glucose. First, the kaempferol biosynthetic pathway was reconstructed via screening various F3H and FLS enzymes. In addition, we demonstrated that amplification of the rate-limiting enzyme AtFLS could reduce the dihydrokaempferol accumulation and improve kaempferol production. Increasing the availability of precursor malonyl-CoA further improved the production of kaempferol and quercetin. Furthermore, the highest amount of 956 mg L^− 1 of kaempferol and 930 mg L^− 1 of quercetin in yeast was reached in fed-batch fermentations. Conclusions: De novo biosynthesis of kaempferol and quercetin in yeast was improved through increasing the upstream naringenin biosynthesis and debugging the flux-limiting enzymes together with fed-batch fermentations, up to gram per liter level. Our work provides a promising platform for sustainable and scalable production of kaempferol, quercetin and compounds derived thereof.

Verapamil inhibits Candida albicans morphogenesis, adhesion and gastrointestinal colonization, and influences both expression and transport of morphogenesis-rel

Squalene, a linear triterpene compound characterized by its distinctive isoprenoid backbone with six transisoprene units, is widely used in the medicinal, nutraceutical, and cosmetic industries. The escalating global demand for squalene, coupled with growing ethical concerns over shark-derived sources and the inherent limitations of plant extraction (low yield) and chemical synthesis (environmental burden), has propelled microbial biosynthesis as a sustainable alternative. While substantial progress has been made in elucidating the mevalonate pathway and regulatory mechanisms of squalene biosynthesis, achieving industrially viable titers through microbial platforms remains an unresolved challenge. This review systematically summarizes recent advances in squalene biosynthesis using yeast chassis, with a focus on metabolic engineering strategies implemented in Saccharomyces cerevisiae and Yarrowia lipolytica. Furthermore, we elaborated on how squalene yields a diverse array of downstream derivatives through intricate enzymatic reactions. These derivatives—including triterpenoid saponins, triterpenoid acids, and steroids—exhibit significant applications in the pharmaceutical, nutraceutical, and cosmetic sectors. By integrating systems metabolic engineering with emerging synthetic biology tools, this work provides a roadmap for advancing strain engineering toward economically feasible squalene biomanufacturing.

With mounting concerns over finite fossil fuel reserves and climate change, increasing attention is being paid to an emerging bioeconomy