Unexpected proteins involved in the regulation of secondary metabolism in Myxococcus xanthus DK1622.

Regulating secondary metabolite (SM) in Myxococcus xanthus bears the potential to influence the formation of important natural products with various biological activities. The authors of this study have previously found that the detectable levels of two proteins (4-hydroxyphenylpyruvate dioxygenase [HppD] and a Hsp90-like protein  [HtpG]) are affected by ROK inactivation. As evidence, the current study was designed to elucidate the possible role of these two proteins in regulating the SMs' biosynthesis in this bacterium.

Based on Serum Pharmacochemistry and Metabolomics Studied the Pharmacodynamic Material Basis and Mechanism of Rubi Fructus (Fupenzi) in Improving the Symptom of Kidney-Yang Deficiency.

Rubi fructus (Fupenzi) is the immature fruit of East China Rubi fructus, which is widely used in medicine, food, health food and other fields. Since ancient times, Fupenzi has been considered to be an important medicine for tonifying the kidney in terms of nourishing the liver and kidney, fixing essence and reducing urine, but its effective components and mechanism are not clear. In this paper, the effective components of Rubi fructus were analyzed by detecting the components of Fupenzi in vivo and in vitro.

Heterologous activation and metabolites identification of the gene cluster from .

The microbial genome remains a huge treasure trove for the discovery of diverse natural products. NRRL23338, the industry producer of erythromycin, has a dozen of biosynthetic gene clusters whose encoding products are unidentified. Heterologous expression of one of the polyketide clusters in B4 chassis resulted in the characterization of its function responsible for synthesizing both 6-methylsalicyclic acid and 6-ethylsalicyclic acid.

Ecliptasaponin A protects heart against acute ischemia-induced myocardial injury by inhibition of the HMGB1/TLR4/NF-κB pathway.

Ethnopharmacological Relevance: Eclipta prostrata (Linn.) is a traditional medicinal Chinese herb that displays multiple biological activities, such as encompassing immunomodulatory, anti-inflammatory, anti-tumor, liver-protective, antioxidant, and lipid-lowering effects. Ecliptasaponin A (ESA), a pentacyclic triterpenoid saponin isolated from Eclipta prostrata (Linn.

Engineering B4 for Enhanced Production of ()-Mellein: A High-Titer Heterologous Biosynthesis Approach.

The natural compound ()-(-)-mellein exhibits antiseptic and fungicidal activities. We investigated its biosynthesis using the polyketide synthase encoded by () from heterologously expressed in B4, a chassis chosen for its fast growth, genetic manipulability, and ample large short-chain acyl-CoA precursor supply. High-level heterologous ()-(-)-mellein yield was achieved by overexpression and duplication.

Engineering of a TetR family transcriptional regulator BkdR enhances heterologous spinosad production in B4 chassis.

Unlabelled: Precursor supply plays a significant role in the production of secondary metabolites. In bacteria, propionyl-, malonyl-, and methylmalonyl-CoA are the most common precursors used for polyketide biosynthesis. Although propionyl-CoA synthetases participate in the propionate assimilation pathway and directly convert propionate into propionyl-CoA, malonyl- and methylmalonyl-CoA cannot be formed using common acyl-CoA synthetases.

SdrR, a LysR-type regulator, responds to the mycobacterial antioxidant defense.

Protection against oxidative stress is a vital defense mechanism for Mycobacterium tuberculosis within the host. However, few transcription factors that control bacterial antioxidant defense are known. Here, we present evidence that SdrR, encoded by the MSMEG_5712 (Ms5712) gene, functions as an oxidative stress response regulator in Mycobacterium smegmatis.

Metabolic Engineering of KT2440 for Biosynthesis of Vanillic Acid.

Vanillic acid (VA), as a plant-derived phenolic acid compound, has widespread applications and good market prospects. However, the traditional production process cannot meet market demand. In this study, KT2440 was used for biosynthesis of VA.

A Faithful Deep Sensitivity Estimation for Accelerated Magnetic Resonance Imaging.

Magnetic resonance imaging (MRI) is an essential diagnostic tool that suffers from prolonged scan time. To alleviate this limitation, advanced fast MRI technology attracts extensive research interests. Recent deep learning has shown its great potential in improving image quality and reconstruction speed.

Biosynthesis of the Plant Coumarin Osthole by Engineered .

Osthole is a coumarin compound found in the traditional Chinese medicine . Extensive studies have shown that osthole exhibits many medicinal properties, and recently, researchers have found that it possesses potent airway-relaxation activity by inhibiting phosphodiesterase 4D activity, making it a potential novel bronchodilator that does not target β2-adrenoceptors for asthma treatment. Here, we report the complete biosynthesis of osthole in engineered yeast.

Metabolic engineering of Yarrowia lipolytica for high-level production of scutellarin.

Scutellarin drugs have been recognized as a key item in the national development of essential clinical emergency drugs for treating cardiovascular and cerebrovascular diseases; therefore, the market demand for scutellarin is growing rapidly. Microbial synthesis based on synthetic biology is a promising method for industrial production of scutellarin. In this study, the highest reported scutellarin titer in the shake flask of 703.

Metabolic engineering for the high-yield production of polydatin in Yarrowia lipolytica.

Polydatin, a glycosylated derivative of resveratrol, has better structural stability and biological activity than resveratrol. Polydatin is the extract of Polygonum cuspidatum, which has various pharmacological effects. Owing to its Crabtree-negative characteristics and high supply of malonyl-CoA, Yarrowia lipolytica was selected to produce polydatin.

Regulation of CRISPR-Associated Genes by Rv1776c (CasR) in .

The CRISPR-Cas system is an adaptive immune system for many bacteria and archaea to defend against foreign nucleic acid invasion, and this system is conserved in the genome of (). Although the CRISPR-Cas system-mediated immune defense mechanism has been revealed in , the regulation of gene expression is poorly understood. In this study, we identified a transcription factor, CasR (CRISPR-associated protein repressor, encoded by ), and it could bind to the upstream DNA sequence of the CRISPR-Cas gene cluster and regulate the expression of genes.

Jointly estimating bias field and reconstructing uniform MRI image by deep learning.

Bias field is one of the main artifacts that degrade the quality of magnetic resonance images. It introduces intensity inhomogeneity and affects image analysis such as segmentation. In this work, we proposed a deep learning approach to jointly estimate bias field and reconstruct uniform image.

Strategies to Improve the Biosynthesis of β-Lactam Antibiotics by Penicillin G Acylase: Progress and Prospects.

β-Lactam antibiotics are widely used anti-infection drugs that are traditionally synthesized via a chemical process. In recent years, with the growing demand for green alternatives, scientists have turned to enzymatic synthesis. Penicillin G acylase (PGA) is the second most commercially used enzyme worldwide with both hydrolytic and synthetic activities toward antibiotics, which has been used to manufacture the key antibiotic nucleus on an industrial level.

Structural and Functional Basis of JAMM Deubiquitinating Enzymes in Disease.

Deubiquitinating enzymes (DUBs) are a group of proteases that are important for maintaining cell homeostasis by regulating the balance between ubiquitination and deubiquitination. As the only known metalloproteinase family of DUBs, JAB1/MPN/Mov34 metalloenzymes (JAMMs) are specifically associated with tumorigenesis and immunological and inflammatory diseases at multiple levels. The far smaller numbers and distinct catalytic mechanism of JAMMs render them attractive drug targets.

PhoP- and GlnR-mediated regulation of metK transcription and its impact upon S-adenosyl-methionine biosynthesis in Saccharopolyspora erythraea.

Background: Erythromycin A (Er A) has a broad antibacterial effect and is a source of erythromycin derivatives. Methylation of erythromycin C (Er C), catalyzed by S-adenosyl-methionine (SAM)-dependent O-methyltransferase EryG, is the key final step in Er A biosynthesis. Er A biosynthesis, including EryG production, is regulated by the phosphate response factor PhoP and the nitrogen response factor GlnR.

Dehydroquinate Synthase Directly Binds to Streptomycin and Regulates Susceptibility of to Streptomycin in a Non-canonical Mode.

Antimicrobial resistance (AMR) represents one of the main challenges in Tuberculosis (TB) treatment. Investigating the genes involved in AMR and the underlying mechanisms holds promise for developing alternative treatment strategies. The results indicate that dehydroquinate synthase (DHQS) regulates the susceptibility of BCG to first-line anti-TB drug streptomycin.

Preventive Effects of Aqueous Extract on High-Fat Diet-Induced Fatty Liver of Mice.

Objective: To investigate the preventive effects of aqueous extract (ICAE) on high-fat diet (HFD)-induced fatty liver of mice and its mechanisms.

Materials And Methods: Twenty-six male KM (Kunming) mice were divided into 3 groups, including the control group ( = 9), fed with normal diet; HFD group ( = 9), fed with HFD; ICAE + HFD group ( = 8), fed with HFD and administered with ICAE (3 g·kg·d) at the same time for 10 weeks. Body weight, liver weight, intra-abdominal and subcutaneous fat weight, serum triglyceride (TG), total cholesterol (TC), and blood glucose were determined to evaluate the preventive effects of ICAE on obesity.

Design and optimization of E. coli artificial genetic circuits for detection of explosive composition 2,4-dinitrotoluene.

The detection of mine-based explosives poses a serious threat to the lives of deminers, and carcinogenic residues may cause severe environmental pollution. Whole-cell biosensors that can detect on-site in dangerous or inaccessible environments have great potential to replace conventional methods. Synthetic biology based on engineering modularity serves as a new tool that could be used to engineer microbes to acquire desired functions through artificial design and precise regulation.

Construction of a p-coumaric and ferulic acid auto-regulatory system in Pseudomonas putida KT2440 for protocatechuate production from lignin-derived aromatics.

Lignin is a robust and underutilized aromatic heteropolymer on earth. The effective valorization of lignin into value-added products is an attractive research topic in lignocellulosic biorefineries. However, a low bioconversion rate, high process cost, low yield, and high toxicity of substrates hinder its further applications.

Reconstruction of Secondary Metabolic Pathway to Synthesize Novel Metabolite in .

Natural polyketides play important roles in clinical treatment, agriculture, and animal husbandry. Compared to natural hosts, heterologous chassis (especially Actinomycetes) have many advantages in production of polyketide compounds. As a widely studied model Actinomycete, is an excellent host to produce valuable heterologous polyketide compounds.

Association between Gene Polymorphisms of T Cell Immunoglobulin Domain and Mucin Domain-3 and Risk of Asthma: A Systematic Review and Meta-analysis.

Previous studies have reported that T cell immunoglobulin domain and mucin domain-3 (TIM-3) 574T>G and 1516G>T are associated with the risk of asthma. However, the results are inconsistent due to the small sample size and varied age in studies. We performed this meta-analysis to systematically evaluated the effect of TIM-3 574T>G and 1516G>T genetic polymorphisms on asthma.