Production of moth sex pheromones for pest control by yeast fermentation

The use of insect sex pheromones is an alternative technology for pest control in agriculture and forestry, which, in contrast to insecticides, does not have adverse effects on human health or environment and is efficient also against insecticide-resistant insect populations. Due to the high cost of chemically synthesized pheromones, mating disruption applications are currently primarily targeting higher value crops, such as fruits. Here we demonstrate a biotechnological method for the production of (Z)-hexadec-11-en-1-ol and (Z)-tetradec-9-en-1-ol, using engineered yeast cell factories. These unsaturated fatty alcohols are pheromone components or the immediate precursors of pheromone components of several economically important moth pests. Biosynthetic pathways towards several pheromones or their precursors were reconstructed in the oleaginous yeast Yarrowia lipolytica, which was further metabolically engineered for improved pheromone biosynthesis by decreasing fatty alcohol degradation and downregulating storage lipid accumulation. The sex pheromone of the cotton bollworm Helicoverpa armigera was produced by oxidation of fermented fatty alcohols into corresponding aldehydes. The resulting yeast-derived pheromone was just as efficient and specific for trapping of H. armigera male moths in cotton fields in Greece as a conventionally produced synthetic pheromone mixture. We further demonstrated the production of (Z)-tetradec-9-en-1-yl acetate, the main pheromone component of the fall armyworm Spodoptera frugiperda. Taken together our work describes a biotech platform for the production of commercially relevant titres of moth pheromones for pest control via yeast fermentation.     

观赏向日葵八氢番茄红素脱氢酶基因PDS的cDNA克隆与表达特性分析

采用RT-PCR和RACE技术从观赏向目葵‘闽葵3号’黄色花瓣中克隆到类胡萝卜素合成途径关键基因HaPDS的cDNA,该cDNA全长2017bp,具有一个1710bp的完整开放阅读框（ORF）,编码一个570个氨基酸的蛋白质。序列分析表明,HaPDS编码的氨基酸序列与其他植物的PDs蛋白具有很高的同源性,在N-端有一个辅助因子结合结构域,C-端有一个类胡萝卜素结合域。系统进化树分析显示,观赏向日葵HaPDS与万寿菊、菊花蛋白亲缘关系较近。实时荧光定量RT-PCR技术分析表明,胁肋路因在花发育的盛花期表达量最高;不同组织中的表达量舌状花瓣〉苞片〉叶片〉绿色管状花〉黑色管状花：随着基因表达量的增加,花色由白色到黄色、金黄色转变。     

Fatty acid remodeling in cellular glycerophospholipids following the activation of human T cells

Changes in fatty acid (FA) and glycerophospholipid (GPL) metabolism associated with cell cycle entry are not fully understood. In this study FA-GPL remodeling was investigated in resting and proliferating primary human T cells. Significant changes were measured in the composition and distribution of FAs in GPLs following receptor activation of human T cells. The FA distribution of proliferating T cells was very similar to that of the human Jurkat T cell line and when the stimulus was removed from proliferating T cells, they stopped proliferating and the FA distribution largely reverted back to that of resting T cells. The cellular content of saturated and monounsaturated FAs was significantly increased in proliferating cells, which was associated with an induction of FA synthase and stearoyl-CoA desaturase-1 gene expression. Additionally, cellular arachidonate was redistributed in GPLs in a distinct pattern that was unlike any other FAs. This redistribution was associated with an induction of CoA-dependent and CoA-independent remodeling. Accordingly, significant changes in the expression of several acyl-CoA synthetases, lysophospholipid acyltransferases, and phospholipase A₂ were measured. Overall, these results suggest that metabolic pathways are activated in proliferating T cells that may represent fundamental changes associated with human cell proliferation.     

Evolution of insect pheromones and their role in reproductive isolation and speciation

The importance for reproductive isolation of a change in the pheromone biosynthetic pathway, resulting in a different pheromone blend, is discussed in Lepidoptera and Diptera. The different sites of pheromone production and the biosynthetic enzymes are briefly reviewed. Two examples of a modification in the pheromone blend leading to reproductive isolation in Lepidoptera are taken as examples: the first, in Ostrinia nubilalis, is involved in the formation of two different populations showing reproductive isolation; the second, in the genus Ostrinia, might be at the origin of the formation of two different species. In both examples, a modification in the function of a desaturase involved in pheromone biosynthesis brings about change in the pheromone blend. In the fruitfly, Drosophila melanogaster, a mutation at a desaturase locus leads to the formation of two populations which differ in their pheromone mixtures and have developed premating isolation. The closely related species, D. melanogaster and D. simulans, differ in their female pheromonal cuticular hydrocarbons. This pheromonal difference is due to two species- and female-specific genes, desatF and eloF. The activity of desatF could account for an effective barrier between these species. All these examples show that a birth and death process of desaturases is at the origin of major shifts in the pheromone blend leading to sexual isolation and speciation.     

4-Bicyclic heteroaryl-piperidine derivatives as potent,orally bioavailable Stearoyl-CoA desaturase-1 (SCD1) inhibitors. Part 1: Urea-based analogs

A new series of urea-based, 4-bicyclic heteroaryl-piperidine derivatives as potent SCD1 inhibitors is described. The structure–activity relationships focused on bicyclic heteroarenes and aminothiazole–urea portions are discussed. A trend of dose-dependent decrease in body weight gain in diet-induced obese (DIO) mice is also demonstrated.     

Nicardipine and Nifedipine Inhibit Fatty Acid Desaturases in Rat Liver Microsomes

Nicardipine and nifedipine, Ca channel blockers, inhibited rat liver microsomal desaturases, though verapamil, methoxyverapamil, cinnarizine, flunarizine, and diltiazem did not. However, nicardipine and nifedipine apparently did not inhibit the fungal desaturation in Mortierella alpina 1S-4. Nicardipine inhibited rat liver microsomal Δ5 desaturase specifically (50% inhibitory concentration, 170 μm), and nifedipine inhibited Δ6 desaturase specifically (78 μm). The inhibition by nicardipine and nifedipine is uncompetitive, the K_i values for Δ5 and Δ6 desaturases being 62 and 44 μm, respectively.