RESUMO
Non-conventional yeasts such as Yarrowia lipolytica, Pichia pastoris, Kluyveromyces marxianus, Rhodosporidium toruloides and Hansenula polymorpha have proven to be efficient cell factories in producing a variety of natural products due to their wide substrate utilization spectrum, strong tolerance to environmental stresses and other merits. With the development of synthetic biology and gene editing technology, metabolic engineering tools and strategies for non-conventional yeasts are expanding. This review introduces the physiological characteristics, tool development and current application of several representative non-conventional yeasts, and summarizes the metabolic engineering strategies commonly used in the improvement of natural products biosynthesis. We also discuss the strengths and weaknesses of non-conventional yeasts as natural products cell factories at current stage, and prospects future research and development trends.
Assuntos
Leveduras/genética , Yarrowia/metabolismo , Edição de Genes , Engenharia MetabólicaRESUMO
6-(Methylsulfinyl) hexyl isothiocyanate (6-MSITC) is an active ingredient present in Wasabi, which is a popular pungent spice used in Japanese cuisine. Our previous studies suggested that the primary antioxidant activity of 6-MSITC may link to other biological activity. This study aimed to clarify how the antioxidant activity of 6-MSITC contributes to preventing overloaded lipid stress in he-patic cell model. HepG2 cells were treated with 6-MSITC at defined concentrations and times in normal medium or in combined fatty acids (CFA) medium, and the targeted proteins were detected by Western blotting. The kinetic data revealed that 6-MSITC activated AMP-activated protein kinase α (AMPKα) and nuclear factor (erythroid-derived 2) like 2 (Nrf2), and then enhanced the protein expression of Forkhead box protein O1 (FOXO1) and Sirtuin1 as well as that of the Nrf2 target proteins, NAD(P)H:quinone oxidoreductase 1 (NQO1) and heme oxygenase (HO-1). Furthermore, lipid metabolic stress was mimicked in HepG2 cells by overloading CFA. 6-MSITC significantly alleviated CFA-induced formation of thiobarbituric acid reactive substances and fat ac-cumulation. Signaling analysis data revealed that 6-MSITC enhanced phosphorylation of AMPKα, upregulated the expression of Nrf2, NQO1, heme oxygenase 1, FOXO1, and Siruin1, and downregulated the expression of PPARα. Taken together, our results suggested that the AMPKα/Nrf2-mediated signaling pathways might be involved in the cytoprotective effects of Wasabi 6-MSITC against metabolic lipid stress.
RESUMO
OBJECTIVE:To investigate blood concentration monitoring data,therapeutic efficacy,toxic reaction and combi-nation of tacrolimus in patients with Allo-HSCT,and to provide reference for clinical application of tacrolimus. METHODS:The blood concentration of tacrolimus in 16 inpatients were monitored with EMIT 3 months after Allo-HSCT. The occurrence of Graft-versus-Host disease(GVHD),ADR and drug combination were analyzed and discussed. RESULTS:A large individual dif-ferences were found in blood concentration of tacrolimus. When blood concentration 20 ng/ml,the occurrence of diabetes,kidney damage and other side effects seems increased. Tacrolimus had a good effect on treatment and prevention of GVHD,and could have an interaction with other drugs. CONCLUSIONS:Blood concentration monitoring of tacrolimus plays an important role on the prevention and treatment of GVHD,and the decrease of side effects such as diabetes and neurotoxicity. The satisfactory blood concentration is 8-20 ng/ml,when there seems a smaller possibility of GVHD and ADR 3 months after Allo-HSCT.