TY - JOUR A1 - de la Cruz, Jorge Gonzalez A1 - Machens, Fabian A1 - Messerschmidt, Katrin A1 - Bar-Even, Arren T1 - Core Catalysis of the Reductive Glycine Pathway Demonstrated in Yeast JF - ACS synthetic biology N2 - One-carbon (C1) compounds are attractive microbial feedstocks as they can be efficiently produced from widely available resources. Formate, in particular, represents a promising growth substrate, as it can be generated from electrochemical reduction of CO2 and fed to microorganisms in a soluble form. We previously identified the synthetic reductive glycine pathway as the most efficient route for aerobic growth on formate. We further demonstrated pathway activity in Escherichia coli after expression of both native and foreign genes. Here, we explore whether the reductive glycine pathway could be established in a model microorganism using only native enzymes. We used the yeast Saccharomyces cerevisiae as host and show that overexpression of only endogenous enzymes enables glycine biosynthesis from formate and CO2 in a strain that is otherwise auxotrophic for glycine. We find the pathway to be highly active in this host, where 0.125 mM formate is sufficient to support growth. Notably, the formate-dependent growth rate of the engineered S. cerevisiae strain remained roughly constant over a very wide range of formate concentrations, 1-500 mM, indicating both high affinity for formate use and high tolerance toward elevated concentration of this C1 feedstock. Our results, as well the availability of endogenous NAD-dependent formate dehydrogenase, indicate that yeast might be an especially suitable host for engineering growth on formate. KW - metabolic engineering KW - synthetic biology KW - one-carbon metabolism KW - carbon labeling KW - tetrahydrofolate KW - glycine cleavage system Y1 - 2019 U6 - https://doi.org/10.1021/acssynbio.8b00464 SN - 2161-5063 VL - 8 IS - 5 SP - 911 EP - 917 PB - American Chemical Society CY - Washington ER - TY - THES A1 - Gonzalez de la Cruz, Jorge T1 - Metabolic engineering of Saccharomyces cerevisiae for formatotrophic growth Y1 - 2019 ER - TY - CHAP A1 - González, Jorge A1 - Casacuberta, Francisco T1 - Phrase-based finite state models N2 - In the last years, statistical machine translation has already demonstrated its usefulness within a wide variety of translation applications. In this line, phrase-based alignment models have become the reference to follow in order to build competitive systems. Finite state models are always an interesting framework because there are well-known efficient algorithms for their representation and manipulation. This document is a contribution to the evolution of finite state models towards a phrase-based approach. The inference of stochastic transducers that are based on bilingual phrases is carefully analysed from a finite state point of view. Indeed, the algorithmic phenomena that have to be taken into account in order to deal with such phrase-based finite state models when in decoding time are also in-depth detailed. Y1 - 2008 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus-27209 ER - TY - JOUR A1 - Gonzalez-Chavarria, Ivan A1 - Duprat, Felix A1 - Roa, Francisco J. A1 - Jara, Nery A1 - Toledo, Jorge R. A1 - Miranda, Felipe A1 - Becerra, Jose A1 - Inostroza, Alejandro A1 - Kelling, Alexandra A1 - Schilde, Uwe A1 - Heydenreich, Matthias A1 - Paz, Cristian T1 - Maytenus disticha extract and an isolated β-Dihydroagarofuran induce mitochondrial depolarization and apoptosis in human cancer cells by increasing mitochondrial reactive oxygen species JF - Biomolecules N2 - Maytenus disticha (Hook F.), belonging to the Celastraceae family, is an evergreen shrub, native of the central southern mountains of Chile. Previous studies demonstrated that the total extract of M. disticha (MD) has an acetylcholinesterase inhibitory activity along with growth regulatory and insecticidal activities. beta-Dihydroagarofurans sesquiterpenes are the most active components in the plant. However, its activity in cancer has not been analyzed yet. Here, we demonstrate that MD has a cytotoxic activity on breast (MCF-7), lung (PC9), and prostate (C4-2B) human cancer cells with an IC50 (mu g/mL) of 40, 4.7, and 5 mu g/mL, respectively, an increasing Bax/Bcl2 ratio, and inducing a mitochondrial membrane depolarization. The beta-dihydroagarofuran-type sesquiterpene (MD-6), dihydromyricetin (MD-9), and dihydromyricetin-3-O-beta-glucoside (MD-10) were isolated as the major compounds from MD extracts. From these compounds, only MD-6 showed cytotoxic activity on MCF-7, PC9, and C4-2B with an IC50 of 31.02, 17.58, and 42.19 mu M, respectively. Furthermore, the MD-6 increases cell ROS generation, and MD and MD-6 induce a mitochondrial superoxide generation and apoptosis on MCF-7, PC9, and C4-2B, which suggests that the cytotoxic effect of MD is mediated in part by the beta-dihydroagarofuran-type that induces apoptosis by a mitochondrial dysfunction. KW - Maytenus disticha KW - beta-dihydroagarofuran-type sesquiterpene KW - dihydromyricetin KW - dihydromyricetin-3-O-beta-glucoside KW - cytotoxic KW - activity KW - Mitochondrial ROS Y1 - 2020 U6 - https://doi.org/10.3390/biom10030377 SN - 2218-273X VL - 10 IS - 3 PB - MDPI CY - Basel ER - TY - JOUR A1 - Hofman, Maarten P. G. A1 - Hayward, M. W. A1 - Heim, M. A1 - Marchand, P. A1 - Rolandsen, C. M. A1 - Mattisson, Jenny A1 - Urbano, F. A1 - Heurich, M. A1 - Mysterud, A. A1 - Melzheimer, J. A1 - Morellet, N. A1 - Voigt, Ulrich A1 - Allen, B. L. A1 - Gehr, Benedikt A1 - Rouco Zufiaurre, Carlos A1 - Ullmann, Wiebke A1 - Holand, O. A1 - Jorgensen, n H. A1 - Steinheim, G. A1 - Cagnacci, F. A1 - Kroeschel, M. A1 - Kaczensky, P. A1 - Buuveibaatar, B. A1 - Payne, J. C. A1 - Palmegiani, I A1 - Jerina, K. A1 - Kjellander, P. A1 - Johansson, O. A1 - LaPoint, S. A1 - Bayrakcismith, R. A1 - Linnell, J. D. C. A1 - Zaccaroni, M. A1 - Jorge, M. L. S. A1 - Oshima, J. E. F. A1 - Songhurst, A. A1 - Fischer, C. A1 - Mc Bride, R. T. A1 - Thompson, J. J. A1 - Streif, S. A1 - Sandfort, R. A1 - Bonenfant, Christophe A1 - Drouilly, M. A1 - Klapproth, M. A1 - Zinner, Dietmar A1 - Yarnell, Richard A1 - Stronza, A. A1 - Wilmott, L. A1 - Meisingset, E. A1 - Thaker, Maria A1 - Vanak, A. T. A1 - Nicoloso, S. A1 - Graeber, R. A1 - Said, S. A1 - Boudreau, M. R. A1 - Devlin, A. A1 - Hoogesteijn, R. A1 - May-Junior, J. A. A1 - Nifong, J. C. A1 - Odden, J. A1 - Quigley, H. B. A1 - Tortato, F. A1 - Parker, D. M. A1 - Caso, A. A1 - Perrine, J. A1 - Tellaeche, C. A1 - Zieba, F. A1 - Zwijacz-Kozica, T. A1 - Appel, C. L. A1 - Axsom, I A1 - Bean, W. T. A1 - Cristescu, B. A1 - Periquet, S. A1 - Teichman, K. J. A1 - Karpanty, S. A1 - Licoppe, A. A1 - Menges, V A1 - Black, K. A1 - Scheppers, Thomas L. A1 - Schai-Braun, S. C. A1 - Azevedo, F. C. A1 - Lemos, F. G. A1 - Payne, A. A1 - Swanepoel, L. H. A1 - Weckworth, B. A1 - Berger, A. A1 - Bertassoni, Alessandra A1 - McCulloch, G. A1 - Sustr, P. A1 - Athreya, V A1 - Bockmuhl, D. A1 - Casaer, J. A1 - Ekori, A. A1 - Melovski, D. A1 - Richard-Hansen, C. A1 - van de Vyver, D. A1 - Reyna-Hurtado, R. A1 - Robardet, E. A1 - Selva, N. A1 - Sergiel, A. A1 - Farhadinia, M. S. A1 - Sunde, P. A1 - Portas, R. A1 - Ambarli, Hüseyin A1 - Berzins, R. A1 - Kappeler, P. M. A1 - Mann, G. K. A1 - Pyritz, L. A1 - Bissett, C. A1 - Grant, T. A1 - Steinmetz, R. A1 - Swedell, Larissa A1 - Welch, R. J. A1 - Armenteras, D. A1 - Bidder, O. R. A1 - Gonzalez, T. M. A1 - Rosenblatt, A. A1 - Kachel, S. A1 - Balkenhol, N. T1 - Right on track? BT - Performance of satellite telemetry in terrestrial wildlife research JF - PLoS one N2 - Satellite telemetry is an increasingly utilized technology in wildlife research, and current devices can track individual animal movements at unprecedented spatial and temporal resolutions. However, as we enter the golden age of satellite telemetry, we need an in-depth understanding of the main technological, species-specific and environmental factors that determine the success and failure of satellite tracking devices across species and habitats. Here, we assess the relative influence of such factors on the ability of satellite telemetry units to provide the expected amount and quality of data by analyzing data from over 3,000 devices deployed on 62 terrestrial species in 167 projects worldwide. We evaluate the success rate in obtaining GPS fixes as well as in transferring these fixes to the user and we evaluate failure rates. Average fix success and data transfer rates were high and were generally better predicted by species and unit characteristics, while environmental characteristics influenced the variability of performance. However, 48% of the unit deployments ended prematurely, half of them due to technical failure. Nonetheless, this study shows that the performance of satellite telemetry applications has shown improvements over time, and based on our findings, we provide further recommendations for both users and manufacturers. Y1 - 2019 U6 - https://doi.org/10.1371/journal.pone.0216223 SN - 1932-6203 VL - 14 IS - 5 PB - PLoS CY - San Fransisco ER -