Long-term intake of sulforaphene alleviates D-galactose-induced skin senescence by activating AMPK-Sirt 1 pathway.

D-Galactose (D-gal) accumulation triggers the generation of oxygen free radicals, resulting in skin aging. Sulforaphene (SFE), an isothiocyanate compound derived from radish seeds, possesses diverse biological activities, including protective effects against inflammation and oxidative damage. This investigation delves into the antioxidant impact of SFE on age-related skin injury. In vivo experiments demonstrate that SFE treatment significantly improves the macro- and micro-morphology of dorsal skin. It effectively diminishes the elevation of oxidative stress biomarkers in mice skin tissue treated with D-gal, concurrently enhancing the activity of antioxidant enzymes. Additionally, SFE mitigates collagen mRNA degradation, lowers pro-inflammatory cytokine levels, and downregulates MAPK-related protein expression in the skin. Moreover, SFE supplementation reduces lipid metabolite levels and elevates amino acid metabolites, such as L-cysteine and L-histidine. These findings suggest that SFE holds promise as a natural remedy to mitigate aging induced by oxidative stress.

New Insight into the Potential Protective Function of Sulforaphene against ROS-Mediated Oxidative Stress Damage In Vitro and In Vivo.

Sulforaphene (SFE) is a kind of isothiocyanate isolated from radish seeds that can prevent free-radical-induced diseases. In this study, we investigated the protective effect of SFE on oxidative-stress-induced damage and its molecular mechanism in vitro and in vivo. The results of cell experiments show that SFE can alleviate D-gal-induced cytotoxicity, promote cell cycle transformation by inhibiting the production of reactive oxygen species (ROS) and cell apoptosis, and show a protective effect on cells with H2O2-induced oxidative damage. Furthermore, the results of mice experiments show that SFE can alleviate D-galactose-induced kidney damage by inhibiting ROS, malondialdehyde (MDA), and 4-hydroxyalkenals (4-HNE) production; protect the kidney against oxidative stress-induced damage by increasing antioxidant enzyme activity and upregulating the Nrf2 signaling pathway; and inhibit the activity of pro-inflammatory factors by downregulating the expression of Toll-like receptor 4 (TLR4)-mediated inflammatory response. In conclusion, this research shows that SFE has antioxidant effects, providing a new perspective for studying the anti-aging properties of natural compounds.

Redesigning regulatory components of quorum-sensing system for diverse metabolic control.

Quorum sensing (QS) is a ubiquitous cell-cell communication mechanism that can be employed to autonomously and dynamically control metabolic fluxes. However, since the functions of genetic components in the circuits are not fully understood, the developed QS circuits are still less sophisticated for regulating multiple sets of genes or operons in metabolic engineering applications. Here, we discover the regulatory roles of a CRP-binding site and the lux box to -10 region within luxR-luxI intergenic sequence in controlling the lux-type QS promoters. By varying the numbers of the CRP-binding site and redesigning the lux box to -10 site sequence, we create a library of QS variants that possess both high dynamic ranges and low leakiness. These circuits are successfully applied to achieve diverse metabolic control in salicylic acid and 4-hydroxycoumarin biosynthetic pathways in Escherichia coli. This work expands the toolbox for dynamic control of multiple metabolic fluxes under complex metabolic background and presents paradigms to engineer metabolic pathways for high-level synthesis of target products.

Rewiring the microbial metabolic network for efficient utilization of mixed carbon sources.

Carbon sources represent the most dominant cost factor in the industrial biomanufacturing of products. Thus, it has attracted much attention to seek cheap and renewable feedstocks, such as lignocellulose, crude glycerol, methanol, and carbon dioxide, for biosynthesis of value-added compounds. Co-utilization of these carbon sources by microorganisms not only can reduce the production cost but also serves as a promising approach to improve the carbon yield. However, co-utilization of mixed carbon sources usually suffers from a low utilization rate. In the past few years, the development of metabolic engineering strategies to enhance carbon source co-utilization efficiency by inactivation of carbon catabolite repression has made significant progress. In this article, we provide informative and comprehensive insights into the co-utilization of two or more carbon sources including glucose, xylose, arabinose, glycerol, and C1 compounds, and we put our focus on parallel utilization, synergetic utilization, and complementary utilization of different carbon sources. Our goal is not only to summarize strategies of co-utilization of carbon sources, but also to discuss how to improve the carbon yield and the titer of target products.

Extending the shikimate pathway for microbial production of maleate from glycerol in engineered Escherichia coli.

Maleate is one of the most important unsaturated four-carbon dicarboxylic acids. It serves as an attractive building block in cosmetic, polymer, and pharmaceutical industries. Currently, industrial production of maleate relies mainly on chemical synthesis using benzene or butane as the starting materials under high temperature, which suffers from strict reaction conditions and low product yield. Here, we propose a novel biosynthetic pathway for maleate production in engineered Escherichia coli. We screened a superior salicylate 5-hydroxylase that can catalyze hydroxylation of salicylate into gentisate with high conversion rate. Then, introduction of salicylate biosynthetic pathway and gentisate ring cleavage pathway allowed the synthesis of maleate from glycerol. Further optimizations including enhancement of precursors supply, disruption of competing pathways, and construction of a pyruvate recycling system, boosted maleate titer to 2.4 ± 0.1 g/L in shake flask experiments. Subsequent scale-up biosynthesis of maleate in a 3-L bioreactor under fed-batch culture conditions enabled the production of 14.5 g/L of maleate, indicating a 268-fold improvement compared with the titer generated by the wildtype E. coli strain carrying the entire maleate biosynthetic pathway. This study provided a promising microbial platform for industrial level synthesis of maleate, and demonstrated the highest titer of maleate production in microorganisms so far.

Metabolic Engineering of Microorganisms for the Production of Flavonoids.

Flavonoids are a class of secondary metabolites found in plant and fungus. They have been widely used in food, pharmaceutical, and nutraceutical industries owing to their significant biological activities, such as antiaging, antioxidant, anti-inflammatory, and anticancer. However, the traditional approaches for the production of flavonoids including chemical synthesis and plant extraction involved hazardous materials and complicated processes and also suffered from low product titer and yield. Microbial synthesis of flavonoids from renewable biomass such as glucose and xylose has been considered as a sustainable and environmentally friendly method for large-scale production of flavonoids. Recently, construction of microbial cell factories for efficient biosynthesis of flavonoids has gained much attention. In this article, we summarize the recent advances in microbial synthesis of flavonoids including flavanones, flavones, isoflavones, flavonols, flavanols, and anthocyanins. We put emphasis on developing pathway construction and optimization strategies to biosynthesize flavonoids and to improve their titer and yield. Then, we discuss the current challenges and future perspectives on successful strain development for large-scale production of flavonoids in an industrial level.

Engineering probiotics as living diagnostics and therapeutics for improving human health.

The gut microbiota that inhabit our gastrointestinal tract are well known to play an important role in maintaining human health in many aspects, including facilitating the digestion and absorption of nutrients, protecting against pathogens and regulating immune system. Gut microbiota dysbiosis is associated with a lot of diseases, such as inflammatory bowel disease, allergy, obesity, cardiovascular and neurodegenerative diseases and cancers. With the increasing knowledge of the microbiome, utilization of probiotic bacteria in modulating gut microbiota to prevent and treat a large number of disorders and diseases has gained much interest. In recent years, aided by the continuous development of tools and techniques, engineering probiotic microbes with desired characteristics and functionalities to benefit human health has made significant progress. In this paper, we summarize the recent advances in design and construction of probiotics as living diagnostics and therapeutics for probing and treating a series of diseases including metabolic disorders, inflammation and pathogenic bacteria infections. We also discuss the current challenges and future perspectives in expanding the application of probiotics for disease treatment and detection. We intend to provide insights and ideas for engineering of probiotics to better serve disease therapy and human health.

Quorum Sensing System Used as a Tool in Metabolic Engineering.

Quorum sensing (QS) is a ubiquitous cell-cell communication mechanism in microbes that coordinates population-level cell behaviors, such as biofilm production, virulence, swarming motility, and bacterial persistence. Efforts to engineer QS systems to take part in metabolic network regulation represent a promising strategy for synthetic biology and pathway engineering. Recently, design, construction, and implementation of QS circuits for programmed control of bacterial phenotypes and metabolic pathways have gained much attention, but have not been reviewed recently. In this article, the architectural organizations and genetic contributions of the naturally occurring QS components to understand the mechanisms are summarized. Then, the most recent progress in application of QS toolkits to develop synthetic networks for novel cell behaviors creation and metabolic pathway engineering is highlighted. The current challenges in large-scale application of these QS circuits in synthetic biology and metabolic engineering fields are discussed and future perspectives for further engineering efforts are provided.