Mushrooms are widely distributed around the world and are heavily consumed because of their nutritional value and medicinal properties. Polysaccharides (PSs) are an important component of mushrooms, ...a major factor in their bioactive properties, and have been intensively studied during the past two decades. Monosaccharide composition/combinations are important determinants of PS bioactivities. This review summarizes: (i) monosaccharide composition/combinations in various mushroom PSs, and their relationships with PS bioactivities; (ii) possible biosynthetic pathways of mushroom PSs and effects of key enzymes on monosaccharide composition; (iii) regulation strategies in PS biosynthesis, and prospects for controllable biosynthesis of PSs with enhanced bioactivities.
Although there have been reports showing the modification effect of carbon nanomaterials on asphalt, there are few studies on whether carbon nanomaterials and polymers can have synergistic ...modification effects on asphalt. At the same time, the complex composition of asphalt makes it difficult to determine the interface mechanism between the modifier and the asphalt. In this study, graphene oxide (GO) and styrene-butadiene-styrene block copolymer (SBS) were selected as modifiers. A combined experimental and molecular simulation research method was used to study the synergistic modification effect and the interface mechanism between the modifier and the asphalt. The results show that the modification effect of GO/SBS incorporated into asphalt is significantly superior to that of GO or SBS incorporated individually and GO/SBS has a synergistic modification effect. Although the binding strength between SBS and asphalt is weak, the GO surface (GO (0 0 1)) can simultaneously bind with SBS and asphalt, increasing the binding strength of SBS and asphalt as well as promoting the dispersion of SBS in asphalt, so that GO/SBS shows a synergistic modification effect and improves properties such as low-temperature ductility, rheology and storage stability at macroscopic level. Intercalated and exfoliated structure can be formed between GO side (GO (0 1 0)) and asphalt, which improves the anti-aging properties of the asphalt. Physical bonding is the main interface binding for GO/SBS compound-modified asphalt. GO bonds to asphalt or SBS by hydrogen bonds and there are only dispersion forces between SBS and asphalt, resulting in a higher binding strength between GO and asphalt or SBS than between SBS and asphalt.
The tumor microenvironment plays an important role in the tumor’s progression and metastasis. Therefore, successful alteration of this delicate setting against the tumor’s favor can open a window for ...therapeutic efficacy. We have developed a modality to bring about treatment-induced alterations in the tumor microenvironment by employing the synergistic effects between two drugs. Co-delivery of rapamycin (RAPA), an mTOR inhibitor that may offer notable therapy through antiangiogenic activity, alongside cisplatin can foster significant potency as RAPA sensitizes A375 melanoma cells to cisplatin therapy through microenvironment modulation. However, encapsulation of these drugs into poly(lactic-co-glycolic acid) (PLGA) NPs was inefficient due to the incompatibility between the two free drugs and the polymer matrix. Here, we show cisplatin can be made hydrophobic by coating a nanoprecipitate (cores) of the drug with dioleoylphosphatidic acid (DOPA). These DOPA coated cisplatin cores are compatible with PLGA and can be coencapsulated in PLGA NPs alongside RAPA at a molar ratio to promote synergistic antitumor activity. The presence of the cisplatin cores significantly improved the encapsulation of RAPA into PLGA NPs. Furthermore, PLGA NPs containing both cisplatin cores and RAPA induced significant apoptosis on A375-luc human melanoma cells in vitro. Additionally, they inhibited the growth of A375-luc melanoma in a xenograft tumor model through modulation of the tumor vasculature and permitted enhanced penetration of NPs into the tumor.
Acetoin and 2,3-butanediol (2,3-BD) have a large number of industrial applications. The production of acetoin and 2,3-BD has traditionally relied on oil supplies. Microbial production of acetoin and ...2,3-BD will alleviate the dependence on oil. Acetoin and 2,3-BD are neighboring metabolites in the 2,3-BD metabolic pathway of bacteria. This review summarizes metabolic engineering strategies for improvement of microbial acetoin and 2,3-BD production. We also propose enhancements to current acetoin and 2,3-BD production strategies, by offering a metabolic engineering approach that is guided by systems biology and synthetic biology.
Intermediates such as 4-androstene-3,17-dione (AD) and 1,4-androstadiene-3,17-dione (ADD) have extensive clinical applications in the production of steroid pharmaceuticals. The present study explores ...the effect of two factors in the production of these intermediates in Mycobacterium neoaurum JC-12: the precursor, phytosterol and a molecule that increases AD/ADD solubility, hydroxypropyl-β-cyclodextrin (HP-β-CD). Differentially expressed proteins were separated and identified using 2D gel electrophoresis (2-DE) and matrix assisted laser desorption/ionization time-of-flight/time-of-flight tandem mass spectrometry (MALDI-TOF/TOF-MS/MS). In total, 31 proteins were identified, and improved expression levels of ten proteins involved in metabolism was induced by phytosterol and/or HP-β-CD, which strengthened the stress resistance of the strain. In the presence of phytosterol and/or HP-β-CD, five proteins involved in the synthesis of AD/ADD, acetyl-CoA acetyltransferase (AAT), alcohol dehydrogenase (ADH), enoyl-CoA hydratase (EH) and short-chain dehydrogenase 1 and 2, increased their expression levels. Reverse transcription-quantitative PCR (RT-qPCR) was used to verify the 2-DE results and the transcriptional level of these five proteins. This analysis identified AAT, ADH, EH, and electron transfer flavoprotein subunit α/β as the possible bottlenecks for AD/ADD synthesis in M. neoaurum JC-12, which therefore are suggested as targets for strain modification.
•A comprehensive proteomic analysis of AD/ADD producing M. neoaurum JC-12 at different fermentation conditions is performed.•Herein, the analysis is performed by combing 2DE analysis and mass spectrometry.•This study facilitates an understanding of global regulation mechanisms of M. neoaurum JC-12 under various conditions.•The possible bottlenecks (AAT, ADH, EH, ETF subunit α/β) for AD/ADD synthesis pathway in M. neoaurum JC-12 are identified.
l-Serine is a non-essential amino acid that has wide and expanding applications in industry with a fast-growing market demand. Currently, extraction and enzymatic catalysis are the main processes for ...l-serine production. However, such approaches limit the industrial-scale applications of this important amino acid. Therefore, shifting to the direct fermentative production of l-serine from renewable feedstocks has attracted increasing attention. This review details the current status of microbial production of l-serine from renewable feedstocks. We also summarize the current trends in metabolic engineering strategies and techniques for the typical industrial organisms Corynebacterium glutamicum and Escherichia coli that have been developed to address and overcome major challenges in the l-serine production process.
Identifying exporters for l-serine can reduce l-serine feedback inhibition and therefore enhance l-serine production.
High-throughput screening using biosensors can be developed for l-serine and used for strain engineering.
The split between l-serine consumption for cell growth and extracellular l-serine accumulation can be balanced by tunable control of metabolic flows combined with 13C metabolic flux analysis.
Systems biology methods, including transcriptomics, proteomics, and metabolomics analysis, can be used for identifying targets for optimizing l-serine production.
Genome-scale metabolic models can prove to be useful for systematically identifying genetic targets for improving l-serine production.
To reduce the cost for commercializing l-serine production, it is essential to explore alternative and cheaper carbon sources.
Encapsulation of cisplatin (CDDP) into nanoparticles (NPs) with high drug loading and encapsulation efficiency has been difficult due to the poor solubility of CDDP. However, this barrier has been ...overcome with a reverse microemulsion method appropriating CDDP’s poor solubility to our advantage promoting the synthesis of a pure cisplatin nanoparticle with a high drug loading capacity (approximately 80.8 wt %). Actively targeted CDDP NPs exhibited significant accumulation in human A375M melanoma tumor cells in vivo. In addition, CDDP NPs achieved potent antitumor efficacy through the neighboring effect at a dose of 1 mg/kg when injected weekly via iv without inducing nephrotoxicity. The neighboring effect regards an observation made in vivo when the tumor cells that took up CDDP NPs released active drug following apoptosis. Via diffusion, surrounding cells that were previously unaffected showed intake of the released drug and their apoptosis soon followed. This observation was also made in vitro when A375M melanoma tumor cells incubated with CDDP NPs exhibited release of active drug and induced apoptosis on untreated neighboring cells. However, the neighboring effect was unique to rapidly proliferating tumor cells. Liver functional parameters and H&E staining of liver tissue in vivo failed to detect any difference between CDDP NP treated and control groups in terms of tissue health. By simultaneously promoting an increase in cytotoxicity and a lesser degree of side effects over free CDDP, CDDP NPs show great therapeutic potential with lower doses of drug while enhancing anticancer effectiveness.
The antimicrobial activity of lactic acid bacteria is closely related to its metabolites. Our results showed that Lactobacillus plantarum DY‐6 had the highest antibacterial activities among the seven ...bacteria tested in this study. To fully understand the active antimicrobial substances in L. plantarum DY‐6, the cell‐free supernatant (CFS) were analyzed. Our data indicated that the antibacterial effect of the CFS was positively correlated with the growth of the bacteria, and the main antibacterial substances were lactic acid, acetic acid, propionic acid, caprylic acid, and decyl acid. Finally, this study demonstrated that the antibacterial active substance produced by the lactic acid bacteria could destroy the cell membrane structure of the bacteria, causing bacteria to fail to grow and reproduce normally, thereby exerting a bacteriostatic action. Taken together, our current findings would provide an effective method for rapid screening of antimicrobial substances.
The main antibacterial substances were found to be lactic acid, acetic acid, propionic acid, caprylic acid and decyl acid. The antibacterial active substance produced by the lactic acid bacteria was found to destroy the cell membrane structure of the bacteria, causing bacteria to fail to grow and reproduce normally, thereby exerting a bacteriostatic action.
l-arginine, a semi essential amino acid, is an important amino acid in food flavoring and pharmaceutical industries. Its production by microbial fermentation is gaining more and more attention. In ...previous work, we obtained a new l-arginine producing Corynebacterium crenatum (subspecies of Corynebacterium glutamicum) through mutation breeding. In this work, we enhanced l-arginine production through improvement of the intracellular environment. First, two NAD(P)H-dependent H2O2-forming flavin reductases Frd181 (encoded by frd1 gene) and Frd188 (encoded by frd2) in C. glutamicum were identified for the first time. Next, the roles of Frd181 and Frd188 in C. glutamicum were studied by overexpression and deletion of the encoding genes, and the results showed that the inactivation of Frd181 and Frd188 was beneficial for cell growth and l-arginine production, owing to the decreased H2O2 synthesis and intracellular reactive oxygen species (ROS) level, and increased intracellular NADH and ATP levels. Then, the ATP level was further increased by deletion of noxA (encoding NADH oxidase) and amn (encoding AMP nucleosidase), and overexpression of pgk (encoding 3-phosphoglycerate kinase) and pyk (encoding pyruvate kinase), and the l-arginine production and yield from glucose were significantly increased. In fed-batch fermentation, the l-arginine production and yield from glucose of the final strain reached 57.3g/L and 0.326g/g, respectively, which were 49.2% and 34.2% higher than those of the parent strain, respectively. ROS and ATP are important elements of the intracellular environment, and l-arginine biosynthesis requires a large amount of ATP. For the first time, we enhanced l-arginine production and yield from glucose through reducing the H2O2 synthesis and increasing the ATP supply.
•Two new H2O2-forming flavin reductases from C. glutamicum are identified.•Inactivation of the flavin reductases facilitates L-arginine production.•Increasing the ATP supply facilitates L-arginine production.
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