A perspective review on the biosynthesis of plant-based secondary metabolites and their application as potent drugs

Many phytochemicals and their derived metabolites produced by plants are extensively employed in commercial goods,pharmaceutical products as well as in the environmental and medicalfields.However,these secondary metabolites obtained from plants are in low amounts,and it is difficult to synthesize them at the industrial level.Despite these challenges,they may be utilized for a variety of medicinal products that are either available in the market or are being researched and tested.Secondary metabolites are complex compounds that exhibit chirality.Further,under controlled conditions with elicitors,desired secondary metabolites may be produced from plant cell cultures.This review emphasizes the various aspects of secondary metabolites including their types,synthesis,and applications as medicinal products.The article aims to promote the use of plant secondary metabolites in the management and treatment of various diseases.

Gene expression and metabolite profiles of cotton fiber during cell elongation and secondary cell wall synthesis

Cotton fibers elongate rapidly after initiation of elongation, eventually leading to the deposit of a large amount of cellulose. To reveal features of cotton fiber cells at the fast elongation and the secondary cell wall synthesis stages, we compared the respective transcriptomes and metabolite profiles. Comparative analysis of transcriptomes by cDNA array identified 633 genes that were differentially regulated during fiber development. Principal component analysis （PCA） using expressed genes as variables divided fiber samples into four groups, which are diagnostic of developmental stages. Similar grouping results are also found if we use non-polar or polar metabolites as variables for PCA of developing fibers. Auxin signaling, wall-loosening and lipid metabolism are highly active during fiber elongation, whereas cellulose biosynthesis is predominant and many other metabolic pathways are downregulated at the secondary cell wall synthesis stage. Transcript and metabolite profiles and enzyme activities are consistent in demonstrating a specialization process of cotton fiber development toward cellulose synthesis. These data demonstrate that cotton fiber cell at a certain stage has its own unique feature, and developmental stages of cotton fiber cells can be distinguished by their transcript and metabolite profiles. During the secondary cell wall synthesis stage, metabolic pathways are streamed into cellulose synthesis.

Studies on Agarofurans VIII. Synthesis of the Metabolites of 4-Butyl-a-agarofuran

The structures of five metabolites (2-6) of agarofuran 1 were confirmed by synthesis. The configuration of the secondary hydroxyl in 7 was determined by Horeau抯 method. The configuration of C-2 in compound 4 and 5 was determined by their stereochemistry and NMR.

STUDIES ON THE SYNTHESIS OF DIMETHYI,4-HYDROXY -4'-METHOXY-5,6,5',6'-BISMETHYLENEDIOXYBIPHENYL-2,2'-DICAPBOXYLATE——AN ESSENTIAL METABOLITE OF DDB

This paper reports the total synthesis of dimethyl 4-hydroxy-4’-methoxy-5,6,5’,6’-bismethylenedioxybiphenyl-2,2’-dicarboxylate(Ⅱ). Various conditions for bromination were tried to find the best one for synthesis of the key intermediate compd 6.After Lllmann condensation of 6 with 8 and hydrogenolysis, the title compd Ⅱ was obtained.It was proved to be identical with the isolated metabolite of DDB by spectral data.

A unique role of the pyrimidine de novo synthesis enzyme ODCase in Lysobacter enzymogenes

Bacterial species of the genus Lysobacter are environmentally ubiquitous with strong antifungal biocontrol potential.Heat-stable antifungal factor(HSAF)secreted by the biocontrol bacterium Lysobacter enzymogenes OH11 has broad-spectrum and highly efficient antifungal activity.Studying the biosynthetic regulations of HSAF would lay an important foundation for strain engineering toward improved HSAF production.In this work,we demonstrate that Le0752,an orotidine-5´-phosphate decarboxylase enzyme(ODCase)catalyzing a pivotal step of the UMP de novo biosynthesis pathway,is vital for HSAF-mediated antimicrobial activities and growth of L.enzymogenes OH11,but not for twitching motility.This gene regulates the production of HSAF by affecting the expression of lafB,a key gene in the HSAF biosynthesis operon,through the transcription factor Clp.Interestingly,bioinformatics analysis revealed that Le0752 belongs to the Group III ODCases,whereas its homologs in the closely related genera Xanthomonas and Stenotrophomonas belong to Group I,which contains most ODCases from Gram-positive bacteria,Gram-negative bacteria and cyanobacteria.Moreover,the Group I ODCase PXO_3614 from the Xanthomonas oryzae pv.oryzae PXO99A strain complemented the Le0752 mutant in regulating HSAF-mediated antagonistic activity.Together,these results highlight the important requirement of de novo pyrimidine biosynthetic enzymes for antibiotic HSAF production in L.enzymogenes,which lays an important foundation for improving HSAF production via metabolic flow design and for dissecting the regulatory functions of bacterial ODCases.

Light Intensity Affects Chlorophyll Synthesis During Greening Process by Metabolite Signal from Mitochondrial Alternative Oxidase in Arabidopsis

Although mitochondrial alternative oxidase(AOX)has been proposed to play essential roles in high light stress tolerance,the effects of AOX on chlorophyll synthesis are unclear.Previous studies indicated that during greening,chlorophyll accumulation was largely delayed in plants whose mitochondrial cyanide-resistant respiration was inhibited by knocking out nuclear encoded AOX gene.Here we show that this delay of chlorophyll accumulation was more significant under high light condition.Inhibition of cyanide-resistant respiration was also accompanied by the increase of plastid NADPH/NADP^+ratio,especially under high light treatment which subsequently blocked the import of multiple plastidial proteins,such as some components of the photosynthetic electron transport chain,the Calvin-Benson cycle enzymes and malate/oxaloacetate shuttle components.Over expression of AOXla rescued the aoxla mutant phenotype,including the chlorophyll accumulation during greening and plastidial protein import.It thus suggests that light intensity affects chlorophyll synthesis during greening process by a metabolic signal,the AOX-derived plastidial NADPH/NADP^+ratio change.And our results thus revealed a molecular mechanism of chloroplast-mitochondria interactions.

Synthesis of the major metabolites of Tolvaptan

Tolvaptan is a nonpeptide arginine vasopressin （AVP） V2-receptor antagonist and used in the treatment of heart failure, cirrhosis, syndrome of inappropriate antidiuretic hormone secretion or other high-volume capacity of hyponatremia. The metabolites of tolvaptan are mainly produced by CYP3A4, including two major compounds named DM-4103 and DM-4107. Herein, the chemical synthesis of those two metabolites is described in this article for further study.

Prodigiosin from Serratia:Synthesis and potential applications

Prodigiosin is a red pigment with a pyrrolylpyrromethane skeleton.It is mainly produced by bacterial strains belonging to the Serratia genus,but also by some other genera,including Streptomyces and Vibrio.Within the genus Serratia,the pigment is generally produced as a virulence factor.However,it also has many important beneficial biological activities such as immunosuppressive and anti-proliferative activities.Moreover,the pigment has many industrial applications in textile and cosmetics.In this mini-review,we discuss the genetic and molecular mechanisms supporting prodigiosin synthesis and production from the Serratia genus,as well as its potential applications.

Why antibiotics: A comparative evaluation of different hypotheses for the natural role of antibiotics and an evolutionary synthesis

Although secondary metabolites with antimicrobial and other bioactivities are explored extensively, the natural or ecological role(s) of secondary metabolites is not yet clearly known. We review here the different hypotheses for the ecological role of antibiotics, with particular focus on the genus Streptomyces which is unparalleled in the richness of secondary metabolites. We first lay down our expectations from an ecological hypothesis for antibiotics and then weigh the six predominant hypotheses against them including antibiotics as weapons in competition, as aid in sporulation, as bartered benefits in symbioses, as signal molecules in community homeostasis, as weapons in predation and as metabolic waste or bi-products. The analysis shows that no single hypothesis meets all the expectations. While the waste or bi-product hypothesis can safely be eliminated all others have some evidence in support. It is possible therefore that antibiotics serve a multitude of ecological functions and it is possible to visualize a pathway for the radiating functions. According to this synthesis antibiotics evolved primarily as weapons in predation on other microorganisms. The inevitable co-evolution with prey species led to diversification of the genes and pathways. Some of the secondary metabolites eventually radiated to acquire other functions such as competition between predators. Some secondary metabolites evolved animal toxicity as a mutualistic barter to protect the symbiotic partner from grazing/predation by animals. Transcription modulation primarily evolved as activation of defense mechanisms by the prey which may have later radiated to serve interspecies signaling functions. The synthesis successfully links different functions of antibiotics with logical coherence.

三种砜吡草唑主要代谢物的合成

为了满足除草剂代谢物毒理试验的需求,本研究设计并优化了砜吡草唑的3个主要代谢物M1、M3和M4的合成路径。通过全新的合成路径,以1-甲基-3-三氟甲基-4-氯甲基-5-二氟甲氧基-1-H-吡唑为起始原料,经过一系列反应步骤,成功合成了M1和M3。以2-甲基-2-丙烯酸和溴肟为原料,经过一系列反应后成功合成M4。通过核磁共振氢谱、液相质谱和高效液相色谱等方法对代谢物的结构和纯度进行了确定。经过优化合成工艺,M1、M3和M4的产率分别达到了76.9%、82.5%和70.1%。合成的代谢物纯度可达97%以上。本研究首次从合成路线的角度出发,成功设计并制备了这3种砜吡草唑代谢物,为农药登记和农残质检等领域提供了重要的研究基础。

抗烟草PVY生防细菌D3-1的筛选鉴定及活性物质分析

由马铃薯Y病毒(Potato virus Y,PVY)引起的病毒病在烟草种植地区大面积发生,对烟草品质和产量产生重大影响。采用半叶枯斑法筛选出对烟草PVY防治效果优良的生防细菌D3-1,对PVY的枯斑抑制率达99.71%,经形态学、生理生化特性以及16Sr DNA序列鉴定其为解淀粉芽胞杆菌Bacillus amyloliquefaciens。菌株D3-1具有广谱的抑菌能力,可抑制病原真菌和细菌生长,菌株D3-1发酵液(1×10^(9)CFU/m L)对烟草PVY的田间防治效果为63.67%。全基因组测序分析发现菌株D3-1基因组含有表面活性素surfactin、丰原素fengycin、嗜铁素bacillibactin等12种具有抑菌作用的次生代谢产物合成基因簇,经HPLC-MS定性分析确定了表面活性素surfactin和丰原素fengycin等32个脂肽类提取物。菌株D3-1对PVY有良好防治效果,具有作为防治烟草PVY生防菌剂的潜力。

武陵山放线菌多样性

【目的】为了探究武陵山放线菌多样性,以便从新放线菌菌株中发现新的潜在药物先导化合物。【方法】从武陵山采集280份土样,采用纯培养的方法,用4种培养基分离到1134株放线菌。选择其中30株代表菌进行了初步分类鉴定;以3株细菌和7株农作物致病真菌作为指示菌,检测其抑菌活性;利用特异性引物扩增的方法,检测是否具有聚酮合酶(PKSⅠ、PKSⅡ)基因、非核糖体多肽合成酶(NRPS)基因和多烯类化合物合成酶(CYP)基因。【结果】分离到的武陵山放线菌中,链霉菌占70%以上,还有小单孢菌等8个科13个属,其中有5个菌株是潜在的新种。选取的30株实验菌对细菌、真菌有不同程度的抗菌活性;其中含有4类化合物合成基因的菌株占23%～60%。【结论】武陵山原始森林土壤中,放线菌多样性很丰富,且存在很多未开发的稀有类群。有抑菌活性的菌株,可用于进一步的药物开发利用。

米非司酮17位侧链代谢物的合成

米非司酮17位侧链代谢物［17β-羟基-11β-（4-二甲氨基苯基)-17α-(1-丙炔醇基）-4．9雌甾二烯-3-酮(4)]是米非司酮口服后主要代谢物之一。本文以3，3-乙二氧基-5(10)，9（11）-雌甾二烯-17-酮（5）为起始物，经环氧化、11β位芳香烃化、17位丙炔醇化、水解制得目标产物(4），中间体和产品均以红外、核磁共振等波谱数据确证结构。

杜仲次生代谢物的研究进展

详细介绍了贵重药材杜仲所含的各种次生代谢物以及各自的功效 ,其中重要次生代谢物松脂素二葡萄糖苷是降压的主要成分 ,环烯醚萜类的桃叶珊瑚苷具有预防和治疗肿瘤、强效抗菌、利尿等功效 ,绿原酸抗菌作用明显 ,对消化系统、血液系统和生殖系统均有药理作用 ;重点阐述了运用植物组织培养法这一新兴生物技术生产杜仲有效成分 (桃叶珊瑚苷、绿原酸 )的研究现状 ,为解决杜仲药源紧缺问题提供了科学依据 ;

植物次生代谢物积累量影响因素分析

针对植物次生代谢物合成积累规律研究中经常出现结论不相一致的问题进行了系统分析,根据作者的研究实践和对文献资料的综合分析认为,其主要原因是在采收分析样品时忽视了地域、立地、个体、品系、年龄、采样部位、采样时期、样品贮存时间等差异因素对植物次生代谢物合成积累的干扰,特别是对个体差异因素的影响认识不足。但是,这些因素所产生的植物次生代谢物合成积累差异性,是植物遗传学(基因型杂合)、生态学(环境差异)特性所引起的,是客观存在。如果在采样过程中忽视了上述因素,测试样品来源(采样)不在同一水平,其测试数据的分析比较就失去了一致性、可比性的前提条件,即使植物次生代谢物含量测试方法精确一致,其结论也不符合客观规律。因此,在进行植物次生代谢物合成积累规律研究时,排除上述干扰因素的样品来源(采样)是至关重要的。

沙雷氏菌抗生性次级代谢产物合成机制

沙雷氏菌(Serratia)是一类重要的生防菌,能分泌多种抗生性代谢产物,如灵菌红素、脂肽、碳青霉烯、几丁质酶、异硫霉素、硝吡咯菌素、水解酶、大环内酯类抗生素、嗜铁素等,从而抑制不同植物病原真菌的生长。总结了沙雷氏菌中已报道的抗生性次级代谢产物生物合成机制,重点阐述了次生代谢产物的功能、合成途径等的新进展,同时对沙雷氏菌在生物防治中的应用和其作为生防菌剂的前景进行展望。

鸢尾酮的制备

鸢尾酮是从鸢尾植物中提取的鸢尾油的特征香气成分,广泛应用于食品和烟草工业中。鸢尾酮主要有α,β和γ三种异构体。本文概述了鸢尾酮的制备方法,包括植物提取法、生物技术法和化学合成法。植物提取法是获得鸢尾酮最直接和简便的方法,但鸢尾植物资源有限,很难满足市场需求。生物技术法能在温和的条件下制备鸢尾酮,但是稳定的菌种筛选是其面临的主要问题。化学合成法是鸢尾酮的主要制备方法,本文重点综述了以植物次生代谢物和石化产品为原料合成鸢尾酮,并对不同制备方法的优缺点进行了评述。因工艺路线长、反应条件苛刻、产率低,多数合成路线仍处于实验室研究阶段,所以研究合成步骤少,反应条件温和、收率和选择性高的工艺路线成为了急需解决的问题。

孕酮受体拮抗剂米非司酮衍生物的合成

为寻找单一的孕酮受体拮抗剂，以米非司酮为先导物，３－乙撑二氧基－５（１０），９（１１）－雌甾二烯－３－酮为原料，经环氧化、格氏加成，加成，还原，水解５步反应，设计并合成了８个目的物及１２个中间体，均未见文献报道，其结构均经红外、核磁及质谱确证。

合成4-雄甾烯-3,17-二酮-19-酸的工艺改进

以米非司酮中间体Ⅱ(19-羟基-4-雄甾烯-3,17-二酮)为原料,2,2,6,6-四甲基哌啶氧(自由基)为催化剂,磷酸盐为缓冲溶液,亚氯酸钠为氧化剂制得米非司酮中间体Ⅰ——4-雄甾烯-3,17-二酮-19-酸,产率80%,其结构经1H NMR,13C NMR和MS确证。

阿苯哒唑硫氧化代谢产物的合成及电喷雾质谱分析

目的合成阿苯哒唑硫氧化物 ,研究阿苯哒唑及其硫氧化物的质谱断裂途径。方法在室温条件下 ,使用过氧化氢将阿苯哒唑氧化成相应的亚砜和砜 ,用硅胶柱层析方法进行分离纯化。采用电喷雾质谱法检测阿苯哒唑及合成产物。结果一次反应同时制得 2种产物 ,[5 (丙基亚砜基 ) 1H 苯并咪唑 2 基 ]氨基甲酸甲酯 (Ⅱ )和 [5 (丙砜基 ) 1H 苯并咪唑 2 基 ]氨基甲酸甲酯 (Ⅲ )经质谱检测其准分子离子峰分别为m/z 2 82和m/z 2 98。结论阿苯哒唑及其 2种氧化产物质谱断裂方式存在共性 ,易生成 [M +H - 32 ]+ 或 [M +H - 4 2 ]+ 的特征碎片离子 。