Advances on the production of organic acids by yeast / 生物工程学报

Organic acids are organic compounds that can be synthesized using biological systems. They often contain one or more low molecular weight acidic groups, such as carboxyl group and sulphonic group. Organic acids are widely used in food, agriculture, medicine, bio-based materials industry and other fields. Yeast has unique advantages of biosafety, strong stress resistance, wide substrate spectrum, convenient genetic transformation, and mature large-scale culture technology. Therefore, it is appealing to produce organic acids by yeast. However, challenges such as low concentration, many by-products and low fermentation efficiency still exist. With the development of yeast metabolic engineering and synthetic biology technology, rapid progress has been made in this field recently. Here we summarize the progress of biosynthesis of 11 organic acids by yeast. These organic acids include bulk carboxylic acids and high-value organic acids that can be produced naturally or heterologously. Finally, future prospects in this field were proposed.

Application of virus-induced gene silencing technology to investigate the phytochrome metabolism mechanism: a review / 生物工程学报

Color is an important indicator for evaluating the ornamental traits of horticultural plants, and plant pigments is a key factor affecting the color phenotype of plants. Plant pigments and their metabolites play important roles in color formation of ornamental organs, regulation of plant growth and development, and response to adversity stress. It has therefore became a hot topic in the field of plant research. Virus-induced gene silencing (VIGS) is a vital genomics tool that specifically reduces host endogenous gene expression utilizing plant homology-dependent defense mechanisms. In addition, VIGS enables characterization of gene function by rapidly inducing the gene-silencing phenotypes in plants. It provides an efficient and feasible alternative for verifying gene function in plant species lacking genetic transformation systems. This paper reviews the current status of the application of VIGS technology in the biosynthesis, degradation and regulatory mechanisms of plant pigments. Moreover, this review discusses the potential and future prospects of VIGS technology in exploring the regulatory mechanisms of plant pigments, with the aim to further our understandings of the metabolic processes and regulatory mechanisms of different plant pigments as well as improving plant color traits.

Research progress of the regulatory role of autophagy in metabolic liver diseases / 中华肝脏病杂志

Autophagy is one of several hepatic metabolic processes in which starved cells are supplied with glucose, free fatty acids, and amino acids to produce energy and synthesize new macromolecules. Moreover, it regulates the quantity and quality of mitochondria and other organelles. As the liver is a vital metabolic organ, specific forms of autophagy are necessary for maintaining liver homeostasis. Protein, fat, and sugar are the three primary nutrients that can be altered by different metabolic liver diseases. Drugs that have an effect on autophagy can either promote or inhibit autophagy, and as a result, it can either increase or inhibit the three major nutritional metabolisms that are affected by liver disease. Thus, this opens up a novel therapeutic option for liver disease.

The improvement effect and metabolic mechanism of Echinops sphaerocephalus extract on osteoporosis model rat / 中国药房

OBJECTIVE To study the intervention effect and metabolic mechanism of Mongolian medicine Echinops sphaerocephalus extract on D-galactose-induced osteoporosis. METHODS Thirty-six 12-week-old male Wistar rats were selected and randomly divided into blank group， model group， Gushukang group， E. sphaerocephalus high-dose， medium-dose and low- dose groups， with 6 rats in each group. Except for blank group， other groups were intraperitoneally injected with D-galactose at 120 mg/kg per day. After 8 weeks of continuous injection， E. sphaerocephalus high-dose， medium-dose and low-dose groups were given drugs intragastrically at dose of 878， 439， 219.5 mg/kg， respectively. Gushukang group was given Gushukang 105.1 mg/kg intragastrically， once a day， for consecutive 8 weeks. After last administration， blood was collected from the abdominal aorta. Enzyme-linked immunosorbent assay was used to measure the contents of bone metabolism indexes [hydroxyproline （HYP）， alkaline phosphatase （ALP）] and oxidative stress indexes [total antioxidant capacity （TAOC）， superoxide dismutase （SOD）， malondialdehyde （MDA）] in serum of rats. Positron emission tomography/computedtomography （PET/CT） was used to analyze the changes of bone microstructure in right tibia bone. Meanwhile， metabolomic technology was used to study the regulation effect of E. sphaerocephalus on osteoporosis model rats. RESULTS Compared with blank group， HYP， ALP， MDA， ratio of bone surface to bone volume （BS/BV）， and trabecular separation （Tb·Sp） in model group were significantly increased （P＜0.05）， while TAOC， SOD， bone mineral density （BMD）， bone volume fraction （BVF）， trabecular E-mail：Xpfdc153@163.com thickness （Tb·Th） and trabecular number （Tb·N） were significantly decreased （P＜0.05）. Compared with model group， above indexes of administration groups were all reversed to different extents. The results of metabonomics study showed that after intervened with the extract of E. sphaerocephalus， 18 metabolites such as arachidonic acid， phenylalanine， tyrosine， tryptophan， isoleucine and uric acid in the serum of rats changed significantly， involving 15 metabolic pathways such as arachidonic acid， phenylalanine and tyrosine， of which arachidonic acid metabolism， phenylalanine metabolism and tyrosine metabolism were the main influencing pathways. CONCLUSIONS E. sphaerocephalus extract can effectively improve D-galactose-induced oxidative stress and the deterioration of bone microstructure， which interferes with metabolic pathways such as arachidonic acid metabolism and amino acid metabolism.

Metabolic regulation and drug target discovery researches in China: Progress and prospect / 中国临床药理学与治疗学

Metabolic regulation is an important mechanism by which organisms adapt to changes in the internal and external environment. Metabolic small molecules function as versatile messengers involved in signaling networks and organ crosstalk, which carries great implications for understanding physiological processes, revealing disease mechanisms and discovering drug targets. In this review, we present an overview of the main progresses in metabolic regulation and drug target discovery researches in China, and look forward to its future direction, which may provide a reference for the drug development endeavor based on metabolic regulation.

The crucial role of metabolic regulation in differential hepatotoxicity induced by furanoids in Dioscorea bulbifera / 中国天然药物

Diterpenoid lactones (DLs), a group of furan-containing compounds found in Dioscorea bulbifera L. (DB), have been reported to be associated with hepatotoxicity. Different hepatotoxicities of these DLs have been observed in vitro, but reasonable explanations for the differential hepatotoxicity have not been provided. Herein, the present study aimed to confirm the potential factors that contribute to varied hepatotoxicity of four representative DLs (diosbulbins A, B, C, F). In vitro toxic effects were evaluated in various cell models and the interactions between DLs and CYP3A4 at the atomic level were simulated by molecular docking. Results showed that DLs exhibited varied cytotoxicities, and that CYP3A4 played a modulatory role in this process. Moreover, structural variation may cause different affinities between DLs and CYP3A4, which was positively correlated with the observation of cytotoxicity. In addition, analysis of the glutathione (GSH) conjugates indicated that reactive intermediates were formed by metabolic oxidation that occurred on the furan moiety of DLs, whereas, GSH consumption analysis reflected the consistency between the reactive metabolites and the hepatotoxicity. Collectively, our findings illustrated that the metabolic regulation played a crucial role in generating the varied hepatotoxicity of DLs.

ATP regulation strategy and its application in the synthesis of microbial metabolites / 生物工程学报

Cofactor engineering, as a new branch of metabolic engineering, mainly involves ATP/ADP, NADH/NAD⁺, NADPH/NADP⁺ and other cofactors. Cofactor engineering can maximize metabolic flow by directly regulating the concentration and form of the cofactor of key enzymes in cells, and quickly direct carbon flow to target metabolites. ATP, as an important cofactor, is involved in many enzyme-catalyzed reactions in microbial cells, and leads to the restriction of the distribution of metabolic pathways by connecting or linking them into a complex network. Therefore, ATP regulation strategy is expected to be a favorable tool for industrial strain modification, to improve the concentration and production capacity of target metabolites, strengthen microbial tolerance to the environment and promote substrate utilization rate. The present review focuses on the recently used effective ATP regulation strategies and the effects of ATP regulation on cell metabolism in order to provide references for the efficient construction of microbial cell factories.

Research Development in Biosynthesis and Metabolic Regulation of Tetracyclic Triterpenoid Saponins in Medicinal Plants / 世界科学技术-中医药现代化

Triterpenoid saponins is an important secondary metabolites in medicinal plants, and the tetracyclic triterpenoid saponins, as one of the main categories, have very high medicinal value and market demand. However, there is no systematic review on the research. Thus, the elucidation of the biosynthetic pathway and metabolism of the medicinal plant tetracyclic triterpenoid saponins has important theoretical significance and broad application prospects.In this review, the biosynthetic pathway and metabolic regulation of medicinal plant of tetracyclic triterpenoid saponins were discussed. My focus in this paper was to introduce the research development of several metabolic biosynthetic pathways of tetracyclic triterpenoid saponins centered on dammarane type, and the gene improvement by methods such as metabolic pathway and other technological methods. This study provides references on secondary metabolic framework of medicinal plants of tetracyclic triterpenoid saponins, accurately locating secondary metabolism and its key enzymes, and promoting the sustainable uses of medicinal plant resources.

Traditional Chinese Practice, A Promising Integrative Intervention for Chronic Non-Infectious Disease Management / 中国结合医学杂志

The number of people with chronic diseases rises rapidly in recent years worldwide. Except for drug medication, mind-body exercises are indispensable for chronic disease management. Traditional Chinese practice (TCP), as an integrative intervention, is known as an effective means to keep in good health and fitness, as well as help regulate emotion. This paper introduces the domestic and overseas studies on effectiveness of TCP for chronic diseases, and explores the key action links from three aspects, including functional training of multiple-joint guided by consciousness, relieving psychological risk factors, improving respiratory and digestive function, blood and lymph circulation through respiratory training, and regulation of nerve, metabolic, and immune system. Finally, the authors discussed how to integrate TCP in the chronic disease management, and put forward that the practice methods and evaluation standard should be assessed academically.

Applications progress of stable isotopic tracer technique in metabolic regulation of endogenous substances / 中草药

With the rapid development of high-sensitivity detection methods, stable isotope tracing technique has received increasing attention. Stable isotope tracing technique can accurately track the activity of labeled compounds in the body through the tracer atoms and determine their specific metabolic pathways based on the distribution of isotopic peaks of the intermediate metabolites. By calculating the flux, the metabolic pathways are analyzed to provide a basis for the study of disease mechanism and drug metabolism. In recent years, the technique has a wide application in the field of biomedicine. This paper summarizes the applications of stable isotopic tracer technique in the metabolic regulation of endogenous substances such as carbohydrate metabolism, lipid metabolism, amino acid metabolism, hormone metabolism, nucleic acid metabolism, and so on.