Metabolic Engineering of Shikimic Acid Biosynthesis Pathway for the Production of Shikimic Acid and Its Branched Products in Microorganisms: Advances and Prospects

The shikimate pathway is a necessary pathway for the synthesis of aromatic compounds. The intermediate products of the shikimate pathway and its branching pathway have promising properties in many fields, especially in the pharmaceutical industry. Many important compounds, such as shikimic acid, quinic acid, chlorogenic acid, gallic acid, pyrogallol, catechol and so on, can be synthesized by the shikimate pathway. Among them, shikimic acid is the key raw material for the synthesis of GS4104 (Tamiflu^®), an inhibitor of neuraminidase against avian influenza virus. Quininic acid is an important intermediate for synthesis of a variety of raw chemical materials and drugs. Gallic acid and catechol receive widespread attention as pharmaceutical intermediates. It is one of the hotspots to accumulate many kinds of target products by rationally modifying the shikimate pathway and its branches in recombinant strains by means of metabolic engineering. This review considers the effects of classical metabolic engineering methods, such as central carbon metabolism (CCM) pathway modification, key enzyme gene modification, blocking the downstream pathway on the shikimate pathway, as well as several expansion pathways and metabolic engineering strategies of the shikimate pathway, and expounds the synthetic biology in recent years in the application of the shikimate pathway and the future development direction.     

Optimized Selection of Water Resource Allocation Schemes Based on Improved Connection Entropy in Beijing’s Southern Plain

Increased urbanization has caused problems such as increasing water consumption and the continuous deterioration of the groundwater environment. It is necessary to consider the groundwater quality in the water resource optimization system and increase the rate of reclaimed water development to reduce the amount of groundwater exploitation and achieve sustainable development of water resources. This study used the Daxing District, a region of Beijing’s southern plain, as an example to evaluate water quality by analyzing water quality data of surface and groundwater from 2012 to 2016 and actual water-use schemes from 2006 to 2016. Three groundwater extraction modes were set up based on NO₃–N concentrations, water resources were optimized under three extraction modes, and water resource optimization schemes were determined based on the improved connection entropy. The results show that (1) the surface water quality was poor, and the proportion of V₄ type water in the indexes of NH₃–N and chemical oxygen demand (COD) was the largest. The surface water can only be used for agricultural irrigation. The pollution sources contributing most to NH₃–N and COD were domestic and agricultural pollution sources. (2) The groundwater quality was good. The NO₃–N index was primarily type I–III water, accounting for 95.20% of the total samples. Severe NH₃–N pollution areas were mainly in the northern region, and most regional groundwater can be used for various purposes. (3) Taking 2016 as an example, three groundwater exploitation modes were set to optimize water resource allocation, and the results showed that the rate of groundwater development and NO₃–N pollution decreased significantly after optimization. (4) Connection entropy is an evaluation method that combines connection numbers and entropy, including identify, difference, and opposition entropy. As connection entropy being a kind of complete entropy, which can reflect the difference of the system in different states, based on the improved connection entropy, the connection entropies of optimal water resource allocation and actual water-use schemes were calculated. The connection entropy of groundwater exploitation mode 3 was less than that of groundwater exploitation modes 1 and 2 and actual water-use schemes from 2006 to 2016. Therefore, exploitation mode 3’s water resource optimization scheme was recommended. In the paper, satisfactory results have been obtained. As a kind of complete entropy, connection entropy has great research value in dealing with complex hydrological problems. This study’s research methods and outcomes can provide methodological and theoretical lessons for water management in freshwater-deficient areas.     

Palladium-catalyzed hydrosilylation of ynones to access silicon-stereogenic silylenones by stereospecific aromatic interaction-assisted Si–H activation

Hydrosilylation is one of the most important reactions in synthetic chemistry and ranks as a fundamental method to access organosilicon compounds in industrial and academic processes. However, the enantioselective construction of chiral-at-silicon compounds via catalytic asymmetric hydrosilylation remained limited and difficult. Here we report a highly enantioselective hydrosilylation of ynones, a type of carbonyl-activated alkynes, using a palladium catalyst with a chiral binaphthyl phosphoramidite ligand. The stereospecific hydrosilylation of ynones affords a series of silicon-stereogenic silylenones with up to 94% yield, 20:1 regioselectivity and 98:2 enantioselectivity. The density functional theory(DFT) calculations were conducted to elucidate the reaction mechanism and origin of high degree of stereoselectivity, in which the powerful potential of aromatic interaction in this reaction is highlighted by the multiple C–H-π interaction and aromatic cavity-oriented enantioselectivitydetermining step during desymmetric functionalization of Si–H bond.     

级联二阶非线性铌酸锂全光开关的研制

以基于准位相匹配和频与差频级联二阶非线性[X^(2)：X^(2)]基础上的全光开关的理论分析作指导,进行了周期极化铌酸锂晶体(PPLN)和退火质子交换光波导(APE)的实验制备,利用所研制的PPLN-APE器件,以自行研制的工作波长为1．54μm的被动调Q掺钴铝酸镁激光器作为控制光源,以工作波长为1．5μm的连续二极管激光器为信号光源进行了级联二阶非线性全光开关实验。当控制光峰值功率为3kw,信号光功率为1mW时,实现13％的开关效率,分析了进一步提高全光开关性能的途径。     

A Docosahexaenoic Acid Derivative (N-Benzyl Docosahexaenamide) as a Potential Therapeutic Candidate for Treatment of Ovarian Injury in the Mouse Model

Commonly used clinical chemotherapy drugs, such as cyclophosphamide (CTX), may cause injury to the ovaries. Hormone therapies can reduce the ovarian injury risk; however, they do not achieve the desired effect and have obvious side effects. Therefore, it is necessary to find a potential therapeutic candidate for ovarian injury after chemotherapy. N-Benzyl docosahexaenamide (NB-DHA) is a docosahexaenoic acid derivative. It was recently identified as the specific macamide with a high degree of unsaturation in maca (Lepidium meyenii). In this study, the purified NB-DHA was administered intragastrically to the mice with CTX-induced ovarian injury at three dose levels. Blood and tissue samples were collected to assess the regulation of NB-DHA on ovarian function. The results indicated that NB-DHA was effective in improving the disorder of estrous cycle, and the CTX+NB-H group can be recovered to normal levels. NB-DHA also significantly increased the number of primordial follicles, especially in the CTX+NB-M and CTX+NB-H groups. Follicle-stimulating hormone and luteinizing hormone levels in all treatment groups and estradiol levels in the CTX+NB-H group returned to normal. mRNA expression of ovarian development-related genes was positive regulated. The proportion of granulosa cell apoptosis decreased significantly, especially in the CTX+NB-H group. The expression of anti-Müllerian hormone and follicle-stimulating hormone receptor significantly increased in ovarian tissues after NB-DHA treatment. NB-DHA may be a promising agent for treating ovarian injury.     

The Potential Antidepressant Action of Duloxetine Co-Administered with the TAAR1 Receptor Agonist SEP-363856 in Mice

Here, we explored the possible interaction between duloxetine and SEP-363856 (SEP-856) in depression-related reactions. The results showed that oral administration of duloxetine showed powerful antidepressant-like effects in both the forced swimming test (FST) and the suspension tail test (TST). SEP-856 orally administered alone also exerted an antidepressant-like effect in FST and TST, especially at doses of 0.3, 1, and 10 mg/kg. In addition, duloxetine (15 mg/kg) and SEP-856 (15 mg/kg) both showed antidepressant-like effects in the sucrose preference test (SPT). Most importantly, in the above experiments, compared with duloxetine alone, the simultaneous use of duloxetine and SEP-856 caused a more significant antidepressant-like effect. It is worth noting that doses of drug combination in FST and TST did not change the motor activities of mice in the open-field test (OFT). Thus, duloxetine and SEP-856 seem to play a synergistic role in regulating depression-related behaviors and might be beneficial for refractory depression.     

实现冷原子或冷分子囚禁的双层光阱列阵

提出了一种新颖的实现冷原子或冷分子囚禁的双层光阱方案,它由二元π相位板列阵和会聚透镜列阵所组成,用平面光波通过此光学系统时将在透镜焦平面两侧形成双层光阱.介绍了产生双层光阱的基本原理,分析了光阱光强分布、强度梯度等与光学系统参数间的关系,研究了双层光阱囚禁原子(或分子)的光学偶极势和自发散射速率(包括瑞利散射和拉曼散射)等.该方案不仅可用于多样品原子(或分子)的光学囚禁及全光型玻色一爱因斯坦凝聚(BEC),而且可用于制备新颖的双层2D光学晶格.     

Diels–Alder dimerization of Morita–Baylis–Hillman acetates catalyzed by organocatalysts

DABCO-catalyzed dimerization of Morita–Baylis–Hillman acetates to synthesize a series of 3-alkyl-4-(E)-alkenyl-cyclohex-1-ene-1,4-dicarbonyl compounds in excellent yields with modest to excellent diastereoselectivity is reported. A plausible reaction mechanism is also proposed on the basis of previous literature and preliminary investigation the asymmetric version of the reaction.     

Substrate-controlled and highly stereoselective synthesis of 2-aminobut-2-ene-1, 4-diones

2-Methylthio-substituted 1,4-enediones, obtained from readily available aryl methyl ketones, were reacted with primary or secondary amines to afford the desired 1,4-diaryl-2-aminobut-2-ene-1,4-diones in excellent yields with high Z/E-stereoselectivity.