Rational Biosynthetic Engineering for Optimization of Geldanamycin Analogues

Tailor made : We report the rational biosynthesis of C15 hydroxylated non‐quinone geldanamycin analogues by site‐directed mutagenesis of the geldanamycin polyketide synthase (PKS), together with a combination of post‐PKS tailoring genes. Rational biosynthetic engineering allowed the generation of geldanamycin derivatives, such as DHQ3 illustrated in the figure, which had superior pharmacological properties in comparison to the parent compound.

     

Directed Biosynthesis of Phytotoxic Alkaloids in the Cyanobacterium Nostoc 78–12A

Out of the green! Precursor‐directed biosynthesis allowed for the production of new nostocarboline derivatives that display phytotoxic and algicidal properties—in a phototrophic organism. The mechanism of action includes downregulation of photosynthesis, as demonstrated by chlorophyll‐a fluorescence imaging.

     

色氨酸生物合成的稳态优化

本文研究了色氨酸生物合成的稳态优化.针对色氨酸生物合成过程的三维非线性动力系统,建立了使色氨酸消耗和分泌的综合项最大的稳态优化控制模型.根据IOM方法,将非线性优化问题近似转化为线性优化问题来求解,最后得到了一个稳定而且鲁棒的稳态,在该稳态下,色氨酸产率提高为基本稳态时的9倍,这一数值结果表明了优化算法的实用性和有效性.     

蛋氨酸特异性合成途径关键酶——高丝氨酸O-酰基转移酶的研究进展

在蛋氨酸生物合成过程中,蛋氨酸特异性合成反应的第一步是高丝氨酸酰基化,由高丝氨酸O-酰基转移酶催化,生成酰基高丝氨酸。高丝氨酸O-酰基转移酶受到末端产物蛋氨酸和S-腺苷蛋氨酸的反馈抑制和反馈阻遏,且高温下极易失活,严重影响碳流流向蛋氨酸,是蛋氨酸生物合成的关键酶,因此对高丝氨酸O-酰基转移酶的研究和改造具有重要意义。但目前关于高丝氨酸O-酰基转移酶的改造和研究较少,在微生物代谢途径中,碳流不能过多流入蛋氨酸合成途径,制约了微生物过量积累蛋氨酸,阻碍了发酵法生产蛋氨酸的工业进程。本文简述了高丝氨酸O-酰基转移酶在蛋氨酸生物合成途径中的作用,在介绍该酶的结构、催化机制和研究现状的基础上,提出该酶在反馈抑制和提高稳定性方面的分子改造策略。     

细菌纤维素的生物合成及在食品工业的应用

细菌纤维素是经微生物发酵形成的新型生物合成材料,具有机械强度高、吸水性能好、纯度高、结晶度高等优良特性,广泛应用于食品工业等领域。已报道的产细菌纤维素的细菌有醋酸菌属(Acetobacter)、根瘤菌属(Rhizobium)、八叠球菌属(Sarcina)、土壤杆菌属(Agrobaeterium)、假单胞菌属(Preudomonas)、无色杆菌属(Achromobacter)、固氮菌属(Azotobacter)、气杆菌属(Aerobacter)和产碱菌属(Alcaligenes)这9个属中的某些种,真正能够应用于工业化生产细菌纤维素的只有醋酸菌中的几个种,他们是木醋杆菌(Acetobacter xylinum)、醋化醋杆菌(Acetobacteraceti)、产醋醋杆菌(Acetobacteracotigenum)和巴氏醋杆菌(Acetobacter pastcurianum)。本文通过分析近期国内外与细菌纤维素相关文献,对其高产菌种选育、培养基优化和发酵模式等方面的研究进行综述,并展望其在食品工业中的应用前景,为进一步深入研究细菌纤维素提供理论基础和科学依据。     

麦角硫因机体内的分布与代谢和其在疾病中的作用研究进展

麦角硫因是一种稀有的天然氨基酸类强抗氧化剂,由放线菌、蓝细菌、部分真菌（例如链霉菌、分枝杆菌等）和蘑菇等微生物合成。动物（包括人类）和植物自身不能在体内合成麦角硫因,植物可通过根系从土壤中吸收微生物合成的麦角硫因,而动物可从食物中吸收和积累麦角硫因。人体通过有机阳离子转运蛋白1型从食物中吸收麦角硫因,其广泛分布于人体的细胞和组织中。已有大量研究报道了麦角硫因的合成、自然界中的分布、化学性质、生理功能和其作为抗氧化剂的特性。尽管研究证明麦角硫因在体外具有明显的抗氧化活性和细胞保护作用,但对其在体内的生理功能研究仍有限。本文旨在综述麦角硫因的独特性质、生物合成以及预防疾病的潜力。     

Bioinspired Design of Lysolytic Triterpenoid–Peptide Conjugates that Kill African Trypanosomes

Humans have evolved a natural immunity against Trypanosoma brucei infections, which is executed by two serum (lipo)protein complexes known as trypanolytic factors (TLF). The active TLF ingredient is the primate-specific apolipoprotein L1 (APOL1). The protein has a pore-forming activity that kills parasites by lysosomal and mitochondrial membrane fenestration. Of the many trypanosome subspecies, only two are able to counteract the activity of APOL1; this illustrates its evolutionarily optimized design and trypanocidal potency. Herein, we ask whether a synthetic (syn) TLF can be synthesized by using the design principles of the natural TLF complexes but with different chemical building blocks. We demonstrate the stepwise development of triterpenoid–peptide conjugates, in which the triterpenoids act as a cell-binding, uptake and lysosomal-transport modules and the synthetic peptide GALA acts as a pH-sensitive, pore-forming lysolytic toxin. As designed, the conjugate kills infective-stage African trypanosomes through lysosomal lysis thus demonstrating a proof-of-principle for the bioinspired, forward-design of a synTLF.     

Dietary Fish Oil Alters DNA Methylation of Genes Involved in Polyunsaturated Fatty Acid Biosynthesis in Muscle and Liver of Atlantic Salmon (Salmo salar)

Adequate dietary supply of eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3) is required to maintain health and growth of Atlantic salmon (Salmo salar). However, salmon can also convert α-linolenic acid (18:3n-3) into eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3) by sequential desaturation and elongation reactions, which can be modified by 20:5n-3 and 22:6n-3 intake. In mammals, dietary 20:5n-3 + 22:6n-3 intake can modify Fads2 expression (Δ6 desaturase) via altered DNA methylation of its promoter. Decreasing dietary fish oil (FO) has been shown to increase Δ5fad expression in salmon liver. However, it is not known whether this is associated with changes in the DNA methylation of genes involved in polyunsaturated fatty acid synthesis. To address this, we investigated whether changing the proportions of dietary FO and vegetable oil altered the DNA methylation of Δ6fad_b, Δ5fad, Elovl2, and Elovl5_b promoters in liver and muscle from Atlantic salmon and whether any changes were associated with mRNA expression. Higher dietary FO content increased the proportions of 20:5n-3 and 22:6n-3 and decreased Δ6fad_b mRNA expression in liver, but there was no effect on Δ5fad, Elovl2, and Elovl5_b expression. There were significant differences between liver and skeletal muscle in the methylation of individual CpG loci in all four genes studied. Methylation of individual Δ6fad_b CpG loci was negatively related to its expression and to proportions of 20:5n-3 and 22:6n-3 in the liver. These findings suggest variations in dietary FO can induce gene-, CpG locus-, and tissue-related changes in DNA methylation in salmon.     

脱氮假单胞杆菌耗氧合成V_(B_(12))发酵条件的研究

对脱氮假单胞杆菌(Pseudomonas denitri ficans)耗氧合成V_(B_(12))的培养模式研究表明,分批补料发酵比分批发酵合成V_(B_(12))提高71.42%;其中液糖补料与糖蜜补料在同等条件下,产物浓度前者比后者高出19.08%。最适V_(B_(12))合成的培养条件如种龄、接种量和初始pH值分别为18h,10%和7.0;发酵过程中摇床的转速对V_(B_(12))的合成影响显著,其中最佳转速为260r/min。在以上优化条件下,V_(B_(12))的最高单位能达到140 g/L。     

Sesquiterpenes in grapes and wines: Occurrence,biosynthesis, functionality,and influence of winemaking processes

Grapes are an important global horticultural product, and are mainly used for winemaking. Typically, grapes and wines are rich in various phytochemicals, including phenolics, terpenes, pyrazines, and benzenoids, with different compounds responsible for different nutritional and sensory properties. Among these compounds, sesquiterpenes, a subcategory of the terpenes, are attracting increasing interest as they affect aroma and have potential health benefits. The characteristics of sesquiterpenes in grapes and wines in terms of classification, biosynthesis pathway, and active functions have not been extensively reviewed. This paper summarizes 97 different sesquiterpenes reported in grapes and wines and reviews their biosynthesis pathways and relevant bio‐regulation mechanisms. This review further discusses the functionalities of these sesquiterpenes including their aroma contribution to grapes and wines and potential health benefits, as well as how winemaking processes affect sesquiterpene concentrations.