Emerging evidence has linked the gut microbiome to human obesity. We performed a metagenome-wide association study and serum metabolomics profiling in a cohort of lean and obese, young, Chinese individuals. We identified obesity-associated gut microbial species linked to changes in circulating metabolites. The abundance of Bacteroides thetaiotaomicron, a glutamate-fermenting commensal, was markedly decreased in obese individuals and was inversely correlated with serum glutamate concentration. Consistently, gavage with B. thetaiotaomicron reduced plasma glutamate concentration and alleviated diet-induced body-weight gain and adiposity in mice. Furthermore, weight-loss intervention by bariatric surgery partially reversed obesity-associated microbial and metabolic alterations in obese individuals, including the decreased abundance of B. thetaiotaomicron and the elevated serum glutamate concentration. Our findings identify previously unknown links between intestinal microbiota alterations, circulating amino acids and obesity, suggesting that it may be possible to intervene in obesity by targeting the gut microbiota.

Protein molecules were directly embedded in metal-organic frameworks (MOFs) by a coprecipitation method. The protein molecules majorly embedded on the surface region of MOFs display high biological activities. As a demonstration of the power of such materials, the resulting Cyt c embedded in ZIF-8 showed a 10-fold increase in peroxidase activity compared to free Cyt c in solution and thus gave convenient, fast, and highly sensitive detection of trace amounts of explosive organic peroxides in solution.

Obesity develops when energy intake exceeds energy expenditure. Promoting brown adipose tissue formation and function increases energy expenditure and hence may counteract obesity. Berberine (BBR) is a compound derived from the Chinese medicinal plant Coptis chinensis. Here we show that BBR increases energy expenditure, limits weight gain, improves cold tolerance and enhances brown adipose tissue (BAT) activity in obese db/db mice. BBR markedly induces the development of brown-like adipocytes in inguinal, but not epididymal adipose depots. BBR also increases expression of UCP1 and other thermogenic genes in white and BAT and primary adipocytes via a mechanism involving AMPK and PGC-1α. BBR treatment also inhibits AMPK activity in the hypothalamus, but genetic activation of AMPK in the ventromedial nucleus of the hypothalamus does not prevent BBR-induced weight loss and activation of the thermogenic programme. Our findings establish a role for BBR in regulating organismal energy balance, which may have potential therapeutic implications for the treatment of obesity.

Re-engineering enzymes with high activities in the given environments different from the physiological one has been constantly pursued for application of enzymatic catalysis in industrial biocatalytic processes, pharmaceutical industry, biosensing, etc. Re-engineering enzyme catalysts by chemical approaches, including immobilization and chemical modification, represents a simple but effective route. The unusual phenomenon that immobilized or chemically modified enzymes display higher activities than native enzymes has been observed in both single- and multiple-enzyme systems. Recent achievements in enhancing enzymatic activities in both single-and multiple-enzyme systems by chemical approaches are summarized in this review. We propose that these enhanced enzymatic activities can be attributed to the well-designed specific interactions between immobilization carriers (or chemical modifiers) and enzymes, substrates, or reaction media. In addition to this mechanism, which is applicable for both single- and multiple-enzyme systems, other important factors responsible for enhanced activities of multiple-enzyme systems, including substrate channeling, kinetic matching, and an ordered spatial distribution of enzymes, are also discussed. Understanding the origin of enhanced activity in enzymatic catalysis may provide new insights and inspiration to design efficient enzyme catalysts for practical applications.

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We report a simple precipitation method for the construction of spatially co-localized multi-enzyme systems based on inorganic nanocrystal-protein complexes. A spatially controlled multi-enzyme system exhibits enhanced overall catalytic performance, allowing for sensitive detection of glucose in solution.

The throughput of enzyme cascade reactions could be increased if the environmental conditions could be optimized for each enzyme in the cascade individually. Here, we describe the engineering of the microenvironment of one enzyme (Cytochrome C (abbreviated as Cyt C), which is active under acidic conditions), with respect to pH, so that it operates optimally together with a second enzyme (d-amino acid oxidase, which is active under alkaline conditions). Conjugation of Cyt C with a negatively charged polyelectrolyte lowers the local pH at the Cyt C active site and enables a 10-fold enhancement in cascade throughput.

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