Paclitaxel is a potent and widely used antitumor agent. Considerable worldwide research efforts have been carried out on different production alternatives. Since the description of the first paclitaxel-producing fungi, more than 15 years ago, microorganisms have been investigated as potential alternatives for an environmentally acceptable, relatively simple and inexpensive method to produce paclitaxel. However, in spite of significant research on paclitaxel-producing microorganisms, no commercial fermentation process has been implemented up to now. The aim of this study is to review the present status of research on paclitaxel-producing microorganisms and the ongoing efforts to develop heterologous paclitaxel biosynthesis, and analyze the perspectives of microbial fermentation for paclitaxel production.
The influence of ammonium, phosphate and citrate on astaxanthin production by the yeast Phaffia rhodozyma was investigated. The astaxanthin content in cells and the final astaxanthin concentration increased upon reduction of ammonium from 61 mM to 12.9 mM (from 140 microg/g to 230 microg/g and 1.2 microg/ml to 2.3 microg/ml, respectively). Similarly, both the astaxanthin content and astaxanthin concentration increased by reducing phosphate from 4.8 mM to 0.65 mM (160 microg/g to 215 microg/g and 1.7 microg/ml to 2.4 microg/ml, respectively). Low concentrations of ammonium or phosphate also increased the fatty acid content in cells. By analogy with lipid synthesis in other oleaginous yeasts, an examination of the data for varying nitrogen and phosphate levels suggested that citrate could be the source of carbon for fatty acids and carotenoid synthesis. Supporting this possibility was the fact that supplementation of citrate in the medium at levels of 28 mM or higher notably increased the final pigment concentration and pigment content in cells. Increased carotenoid synthesis at low ammonium or phosphate levels, and stimulation by citrate were both paralleled by decreased protein synthesis. This suggested that restriction of protein synthesis could play an important role in carotenoid synthesis by P. rhodozyma.
The aim of this work was the isolation and taxonomic characterization of endophytic fungi from Taxus globosa at the Sierra Alta Hidalguense, Mexico. A total of 116 fungi were isolated from the bark, branches, leaves and roots of healthy yew trees. Based on morphological characteristics 57 were selected for taxonomic characterization through phylogenetic analysis of their 28S rDNA sequences. The fungal isolates belonged to Ascomycota (77.2%) and Basidiomycota (22.8%). Twelve different fungal groups were Trametes for the first time were isolated from yews; this suggests that T. globosa harbours novel and highly diverse fungi. The Shannon-Weaver and Simpson diversity index values for the overall fungal community were H′=3.139 and 1-D=0.941 respectively.
BackgroundGrowth conditions that bring about stress on Phaffia rhodozyma cells encourage the synthesis of astaxanthin, an antioxidant carotenoid, which protects cells against oxidative damage. Using P. rhodozyma cultures performed with and without copper limitation, we examined the kinetics of astaxanthin synthesis along with the expression of asy, the key astaxanthin synthesis gene, as well as aox, which encodes an alternative oxidase protein.ResultsCopper deficiency had a detrimental effect on the rates of oxygen consumption and ethanol reassimilation at the diauxic shift. In contrast, copper deficiency prompted alcoholic fermentation under aerobic conditions and had a favorable effect on the astaxanthin content of cells, as well as on aox expression. Both cultures exhibited strong aox expression while consuming ethanol, but particularly when copper was absent.ConclusionWe show that the induction of either astaxanthin production, aox expression, or aerobic fermentation exemplifies the crucial role that redox imbalance plays in triggering any of these phenomena. Based on our own results and data from others, we propose a mechanism that rationalizes the central role played by changes of respiratory activity, which lead to redox imbalances, in triggering both the short-term antioxidant response as well as fermentation in yeasts and other cell types.
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