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.
Various biosynthetic pathways have been designed to explore sustainable production of glutarate, an attractive C5 building block of polyesters and polyamides. However, its efficient production has not been achieved in
Escherichia coli
. Here, we use
E. coli
native lysine catabolic machinery for glutarate biosynthesis. This endogenous genes-only design can generate strong metabolic driving force to maximize carbon flux toward glutarate biosynthesis by replenishing glutamate and NAD(P)H for lysine biosynthesis, releasing lysine feedback inhibition, and boosting oxaloacetate supply. We use native transporters to overcome extracellular accumulation of cadaverine and 5-aminovalerate. With these efforts, both high titer (54.5 g L
−1
) and high yield (0.54 mol mol
−1
glucose) of glutarate production are achieved under fed-batch conditions. This work demonstrates the power of redirecting carbon flux and the role of transporters to decrease intermediate accumulation.
Aromatic natural products represent a diverse class of chemicals with great industrial significance. Usually, they serve as the building blocks for production of various polymers, esters, fibers, nutraceuticals, and pharmaceuticals. However, industrial synthesis of aromatic natural products still relies heavily on petroleum-based chemical processes, which are not sustainable and eco-friendly. In the past decades, construction of microbial cell factories that are able to efficiently convert renewable carbon sources into value-added products has made significant progress. This review highlights the recent advances in metabolic engineering efforts for biological production of aromatic natural products and their derivatives. Many novel pathways, enzymes, and products were reported in the literatures but have not yet detailed and informative viewed so far. Our goals are to provide a landscape of current works and present guidelines to address future challenges in biosynthesis of aromatic natural products and their derivatives using engineered microorganisms.
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