Vanillin is a popular flavoring agent widely used around the world. Vanillin is generated by natural extraction, chemical synthesis, or tissue culture technology, but these production methods no ...longer meet the increasing worldwide demand for vanillin. Accordingly, a biotechnological approach may provide an effective replacement route to obtaining vanillin. Processes for environmentally friendly production of vanillin in microorganisms from different carbon sources, such as eugenol, isoeugenol, lignin, ferulic acid, sugars, and waste residues, with high productivity and yield have been developed. However, challenges remain for optimizing the vanillin biosynthesis process and further improving production titer and yield. In this review, successful and applicable strategies for increasing vanillin titer and yield in different microorganisms are summarized. Additionally, perspectives for further optimizing the production of vanillin are discussed.
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With concerns about depletion of fossil fuel and environmental pollution, synthesis of biofuels such as isobutanol from low-cost substrate by microbial cell factories has attracted more and more ...attention. As one of the most promising carbon sources instead of food resources, acetate can be utilized by versatile microbes and converted into numerous valuable chemicals. An isobutanol synthetic pathway using acetate as sole carbon source was constructed in E. coli. Pyruvate was designed to be generated via acetyl-CoA by pyruvate-ferredoxin oxidoreductase YdbK or anaplerotic pathway. Overexpression of transhydrogenase and NAD kinase increased the isobutanol titer of recombinant E. coli from 121.21 mg/L to 131.5 mg/L under batch cultivation. Further optimization of acetate supplement concentration achieved 157.05 mg/L isobutanol accumulation in WY002, representing the highest isobutanol titer by using acetate as sole carbon source. The utilization of acetate as carbon source for microbial production of valuable chemicals such as isobutanol could reduce the consumption of food-based substrates and save production cost. Engineering strategies applied in this study will provide a useful reference for microbial production of pyruvate derived chemical compounds from acetate.
L-phenylalanine is an important aromatic amino acid that is widely used in the area of feed, food additives, and pharmaceuticals. Among the different strategies of L-phenylalanine synthesis, direct ...microbial fermentation from raw substrates has attracted more and more attention due to its environment friendly process and low-cost raw materials. In this study, a rational designed recombinant Escherichia coli was constructed for L-phenylalanine production. Based on wild type E. coli MG1655, multilevel engineering strategies were carried out, such as directing more carbon flux into the L-phenylalanine synthetic pathway, increasing intracellular level of precursors, blocking by-product synthesis pathways and facilitating the secretion of L-phenylalanine. During 5 L fed batch fermentation, recombinant E. coli MPH-3 could produce 19.24 g/L of L-phenylalanine with a yield of 0.279 g/g glucose. To the best of our knowledge, this is one of the highest yields of L-phenylalanine producing E. coli using glucose as the sole carbon source in fed-batch fermentation.
•Calcium citrate followed the second-category spherulitic growth mechanism.•A concentration-dependent spherulitic growth operating space was established.•Calcium citrate spherical products had better ...flowability and tabletability.•The micronized spherical products had great suspension stability.
Calcium citrate, a high-end daily calcium supplement, whose irregular particle morphology leads to poor powder properties, limited food functions, and paste-like suspension problems. This study prepared the spherical calcium citrate by investigating four aspects of this reactive process: side reaction, crystallization, agglomeration, and fragmentation. Consequently, a concentration-dependent spherulitic growth operating space was established, in which reactive crystallization followed the second-category spherulitic growth mechanism depending on supersaturation. Besides, the temperature, stirring rate, and residence time were critical parameters for regulating the spherulite shape and size. These spherulites exhibited improved flowability and tabletability as calcium fortification ingredient, it also had a smoother and more pleasant texture. Furthermore, the micronized spherical powder showed high suspension stability as a calcium supplement during brewing. These spherical particles did not form paste-like suspension. Finally, the success of the scale-up experiments in semi-batch mode raised the possibility of industrialization of spherical calcium citrate.
With advantages of low substrates cost, high optical purity of end products and environmentally friendly fermentation process, microbial production of valuable chemicals grow rapidly. Compared with ...static microbial strain engineering strategies, such as gene deletion, overexpression and mutation, dynamic pathway regulation is a new approach that balances cellular growth and chemical production. Quorum sensing is a natural microbial communication system responsible for cell-density-related cell behaviors. Accordingly, quorum sensing systems can be employed to achieve dynamic regulation in microorganisms without the need for manual intervention or the use of chemical inducers. In this review, natural quorum sensing systems are firstly summarized. Then, recent progress in using quorum sensing circuits in the field of metabolic engineering is highlighted. The current application challenges of quorum sensing systems and future perspectives in microbial synthesis of chemicals are also discussed.
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A new fluorinated nonfullerene acceptor, ITIC‐Th1, has been designed and synthesized by introducing fluorine (F) atoms onto the end‐capping group 1,1‐dicyanomethylene‐3‐indanone (IC). On the one ...hand, incorporation of F would improve intramolecular interaction, enhance the push–pull effect between the donor unit indacenodithieno3,2‐bthiophene and the acceptor unit IC due to electron‐withdrawing effect of F, and finally adjust energy levels and reduce bandgap, which is beneficial to light harvesting and enhancing short‐circuit current density (JSC). On the other hand, incorporation of F would improve intermolecular interactions through CF···S, CF···H, and CF···π noncovalent interactions and enhance electron mobility, which is beneficial to enhancing JSC and fill factor. Indeed, the results show that fluorinated ITIC‐Th1 exhibits redshifted absorption, smaller optical bandgap, and higher electron mobility than the nonfluorinated ITIC‐Th. Furthermore, nonfullerene organic solar cells (OSCs) based on fluorinated ITIC‐Th1 electron acceptor and a wide‐bandgap polymer donor FTAZ based on benzodithiophene and benzotriazole exhibit power conversion efficiency (PCE) as high as 12.1%, significantly higher than that of nonfluorinated ITIC‐Th (8.88%). The PCE of 12.1% is the highest in fullerene and nonfullerene‐based single‐junction binary‐blend OSCs. Moreover, the OSCs based on FTAZ:ITIC‐Th1 show much better efficiency and better stability than the control devices based on FTAZ:PC71BM (PCE = 5.22%).
Single‐junction binary‐blend nonfullerene polymer solar cells based on fluorinated acceptor ITIC‐Th1 afford power conversion efficiency of 12.1%, which is much higher than those of nonfluorinated ITIC‐Th (8.88%) and PC71BM (5.22%) counterparts under the same condition. Moreover, the nonfullerene devices exhibit better thermal stability than the fullerene devices.
A new fluorinated electron acceptor (FINIC) based on 6,6,12,12‐tetrakis(3‐fluoro‐4‐hexylphenyl)‐indacenobis(dithieno3,2‐b;2′,3′‐dthiophene) as the electron‐donating central core and ...5,6‐difluoro‐3‐(1,1‐dicyanomethylene)‐1‐indanone as the electron‐deficient end groups is rationally designed and synthesized. FINIC shows similar absorption profile in dilute solution to the nonfluorinated analogue INIC. However, compared with INIC, FINIC film shows red‐shifted absorption, down‐shifted frontier molecular orbital energy levels, enhanced crystallinity, and more ordered molecular packing. Single‐crystal structure data show that FINIC molecules pack into closer 3D “network” motif through H‐bonding and π–π interaction, while INIC molecules pack into incompact “honeycomb” motif through only π–π stacking. Theoretical calculations reveal that FINIC has stronger electronic coupling and more molecular interactions than INIC. FINIC has higher electron mobilities in both horizontal and vertical directions than INIC. Moreover, FINIC and INIC support efficient 3D exciton transport. PBD‐SF/FINIC blend has a larger driving force for exciton splitting, more efficient charge transfer and photoinduced charge generation. Finally, the organic solar cells based on PBD‐SF/FINIC blend yield power conversion efficiency of 14.0%, far exceeding that of the PBD‐SF/INIC‐based devices (5.1%).
A fused‐ring electron acceptor, FINIC, with fluorination of both end groups and side chains is designed and synthesized, and compared with its nonfluorinated analogue, INIC. FINIC exhibits 3D molecular stacking, exciton transport and charge transport. FINIC‐based organic solar cells yield an efficiency of 14.0%, far exceeding that of the INIC‐based devices (5.1%).
Intravenous chemotherapy (IVC) and intra-arterial chemotherapy (IAC) have become the primary treatments for retinoblastoma; however, some controversy remains over which method is more effective. We ...conducted a meta-analysis to compare the clinical efficacy of IVC and IAC.
We systematically searched literature published on PubMed, Embase, and Cochrane Library up to May 2017. Studies containing either IAC or IVC that reported on efficacy were included. The effects estimate was expressed as a pooled rate with 95% confidence interval (CI), using a fixed-effects or random-effects model.
Twenty-six studies were identified which included 1541 eyes (IAC: 11 trials, 445 eyes; IVC: 16 trials, 1096 eyes). The mean follow-up times were 49.4 months (range, 13.0-105.3 months) for IVC and 21.7 months (range, 8.8-38.7 months) for IAC. For the International Classification of Intraocular Retinoblastoma (ICRB) grading, the overall success rate was higher with IAC than with IVC (75.7% 95%CI: 65.7%-83.6% vs. 69.5% 95%CI: 51.9%-82.8%, P < 0.001). The globe salvage with IAC was higher than with IVC in group D eyes (79.5% 95%CI: 71.8%-85.4% vs. 55.1% 95%CI: 45.6%-64.2%, P < 0.001), but not in groups B (95.8% 95%CI: 57.5%-99.7% vs. 82.5% 95%CI: 58.9%-94.0%, P = 0.163), C (91.3% 95%CI: 65.9%-98.3% vs. 89.0% 95%CI: 69.0%-96.7%, P = 0.212), and E eyes (51.2% 95%CI: 37.0%-65.2% vs. 43.2% 95%CI: 18.3%-72.1%, P = 0.578). IAC and IVC were not significantly different regarding the recurrence and metastasis rates (15.0% vs. 15.4%, P = 0.148 and 2.7% vs. 0.6%, P = 0.194, respectively). For Reese-Ellsworth (RE) grading, IAC had a higher globe salvage in groups IV (90.9% 95%CI: 56.0%-98.7% vs. 66.3% 95%CI: 32.4%-89.0%, P = 0.047) and V eyes (83.2% 95%CI: 72.0%-90.5% vs. 59.9% 95%CI: 43.1%-74.6%, P = 0.003), but not in group I-III eyes (88.6% 95%CI: 58.3%-97.7% vs. 88.1% 95%CI: 76.6%-94.4%, P = 0.244). The overall success rate was higher in IAC than in IVC (87.1% 95%CI: 78.1%-92.7% vs. 77.3% 95%CI: 68.1%-84.4%, P = 0.033).
IAC may be superior to IVC for the treatment of retinoblastoma, with a higher overall success rate and higher globe salvage in group D or groups IV and V eyes.
Amorphous metal‐organic frameworks (MOFs) with aperiodic atomic arrangements, featuring high intrinsic activity and rich active sites, have emerged as promising oxygen evolution reaction (OER) ...catalysts. However, the quantitative structure‐activity relationships (SARs) that determine the OER activity, the key to a rational catalyst design, remain unresolved. Inspired by controllable amorphization engineering, the amorphous MOF structures are rationally constructed as an ideal platform to explore the SAR in catalyzing OER. The mechanistic studies show that the OER activity could be volcano‐shape correlated with either constant adsorption energy difference between OOH* and O* (ΔGOOH* − ΔGO*) or the position of the d band center. The amorphous MOF (Ni8Co2‐BDC), situated close to the volcano summit, possesses an appropriate Ed energy level, which exhibits the balanced intermediates adsorption/desorption ability and consequently results in the boosted catalytic activity and long‐term stability. This work supplies new perspectives to investigate the SAR in amorphous MOF structures, thereby guiding the rational design of advanced OER catalysts.
The controllable amorphization engineering is realized on NixCoy‐metal‐organic frameworks (MOFs) with structural evolution from crystalline to amorphous. The oxygen evolution reaction activity of these MOFs demonstrates a volcano‐shaped correlation with either constant adsorption energy difference between OOH* and O* or calculated d band center. The amorphous Ni8Co2‐MOF, located near the summit of the volcano plot, exhibit superior oxygen evolution reaction performance.
Small‐molecule nonfullerene‐based tandem organic solar cells (OSCs) are fabricated for the first time by utilizing P3HT:SF(DPPB)4 and PTB7‐Th:IEIC bulk heterojunctions as the front and back subcells, ...respectively. A power conversion efficiency of 8.48% is achieved with an ultrahigh open‐circuit voltage of 1.97 V, which is the highest voltage value reported to date among efficient tandem OSCs.
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