Tailoring Corynebacterium glutamicum towards efficient production of plant polyphenols

Corynebacterium glutamicum is an important organism in industrial biotechnology for the microbial production of bulk chemicals, in particular amino acids. Functional integration of plant-derived biosynthetic pathways also allows for the microbial synthesis of various plant polyphenols such as flavonoids or stilbenes either from supplemented phenylpropanoid precursor molecules or directly from glucose. However, similar to other microorganisms engineered for plant polyphenol synthesis, insufficient malonyl-CoA supply is also limiting polyphenol production with C. glutamicum. To date, the antibiotic cerulenin inhibiting fatty acid synthesis is added during microbial cultivations to improve malonyl-CoA availability for product formation at lab-scale. Unfortunately, supplementation of cerulenin is very costly, which prohibits large-scale microbial polyphenol production. Please click Additional Files below to see the full abstract

Have Changes in Systemic Treatment Improved Survival in Patients with Breast Cancer Metastatic to the Brain?

Newly developed systemic treatment regimens might lead to improved survival also in the subgroup of breast cancer patients that harbour brain metastases. In order to examine this hypothesis, a matched pairs analysis was performed that involved one group of patients, which were treated after these new drugs were introduced, and one group of patients, which were treated approximately 10 years earlier. The two groups were well balanced for the known prognostic factors age, KPS, extracranial disease status, and recursive partitioning analysis class, as well as for the extent of brain treatment. The results show that the use of systemic chemotherapy has increased over time, both before and after the diagnosis of brain metastases. However, such treatment was performed nearly exclusively in those patients with brain metastases that belonged to the prognostically more favourable groups. Survival after whole-brain radiotherapy has remained unchanged in patients without further active treatment. It has improved in prognostically better patients and especially patients that received active treatment, where the 1-year survival rates have almost doubled. As these patient groups were small, confirmation of the results in other series should be attempted. Nevertheless, the present results are compatible with the hypothesis that improved systemic therapy might contribute to prolonged survival in patients with brain metastases from breast cancer

Towards Improved Prognostic Scores Predicting Survival in Patients with Brain Metastases: A Pilot Study of Serum Lactate Dehydrogenase Levels

Accurate prognostic information is desirable when counselling patients with brain metastases regarding their therapeutic options and life expectancy. Based on previous studies, we selected serum lactate dehydrogenase (LDH) as a promising factor on which we perform a pilot study investigating methodological aspects of biomarker studies in patients with brain metastases, before embarking on large-scale studies that will look at a larger number of candidate markers in an expanded patient cohort. For this retrospective analysis, 100 patients with available information on LDH treated with palliative whole-brain radiotherapy were selected. A comprehensive evaluation of different LDH-based variables was performed in uni- and multivariate tests. Probably, the most intriguing finding was that LDH kinetics might be more important, or at least complement, information obtained from a single measurement immediately before radiotherapy. LDH and performance status outperformed several other variables that are part of prognostic models such as recursive partitioning analyses classes and graded prognostic assessment score. LDH kinetics might reflect disease behaviour in extracranial metastatic and primary sites without need for comprehensive imaging studies and is a quite inexpensive diagnostic test. Based on these encouraging results, confirmatory studies in a larger cohort of patients are warranted

Мониторинг лесных угодий на основе материалов дистанционного зондирования Обь-Томского междуречья в границах Тимирязевского лесничества

В результате выполнения выпускной квалификационной работы был проведен информационно-аналитический анализ нормативно-правовой документации, изучен лесохозяйственный регламент Тимирязевского лесничества Обь-Томского междуречья Томской области, выбраны источники космической информации с достаточной разрешающей способностью для целей лесного мониторинга, а именно снимки, полученные со спутников Landsat 7, Sentinel 2A. Также рассмотрена методика оценки состояния лесных массивов с использованием ГИС-технологий, определены методы автоматизированного дешифрирования для обработки информации и получения результатов, выполнена классификация растительного покрова по снимкам Landsat 7.As a result of the final qualification work, an information and analytical analysis of legal documentation was conducted, the forestry regulations of the Timiryazev forest district of the Ob-Tomsk interfluve of the Tomsk region were studied, and sources of space information with sufficient resolution for forest monitoring were selected, namely images obtained from Landsat 7 and Sentinel 2A satellites. The method of assessing the state of woodlands using GIS technologies is also considered, methods of automated decryption for processing information and obtaining results are defined, and vegetation cover is classified according to Landsat 7 images

Усовершенствование системы сбора и подготовки газа с применением турбодетандерных установок на Мыльджинском нефтегазоконденсатном месторождении (Томская область)

В ходе работы был проведён расчёт и сравнительный анализ эффективности турбодетандерных агрегатов и дросселей на Мыльджинском нефтегазоконденсатном месторождении. Объектом исследования является турбодетандерный агрегат в системе подготовки газа.Экономический эффект достигается за счёт увеличения эффективности метода низкотемпературной сепарации.Сalculations and the comparative analysis of the efficiency of turboexpander units and throttles at the Myldzhinsky oil and gas condensate field were carried out. The object of research is a turbo expanding assembly in a gas treatment system. Economic effect will be achieved by increasing the degree of efficiency of low-temperature separation

OptPipe - a pipeline for optimizing metabolic engineering targets

International audienceBackground: We propose OptPipe-a Pipeline for Optimizing Metabolic Engineering Targets, based on a consensus approach. The method generates consensus hypotheses for metabolic engineering applications by combining several optimization solutions obtained from distinct algorithms. The solutions are ranked according to several objectives, such as biomass and target production, by using the rank product tests corrected for multiple comparisons. Results: OptPipe was applied in a genome-scale model of Corynebacterium glutamicum for maximizing malonyl-CoA, which is a valuable precursor for many phenolic compounds. In vivo experimental validation confirmed increased malonyl-CoA level in case of sdhCAB deletion, as predicted in silico. Conclusions: A method was developed to combine the optimization solutions provided by common knockout prediction procedures and rank the suggested mutants according to the expected growth rate, production and a new adaptability measure. The implementation of the pipeline along with the complete documentation is freely available at https://github.com/AndrasHartmann/OptPipe

Membrane manipulation by free fatty acids improves microbial plant polyphenol synthesis

Microbial synthesis of nutraceutically and pharmaceutically interesting plant polyphenols represents a more environmentally friendly alternative to chemical synthesis or plant extraction. However, most polyphenols are cytotoxic for microorganisms as they are believed to negatively affect cell integrity and transport processes. To increase the production performance of engineered cell factories, strategies have to be developed to mitigate these detrimental effects. Here, we examine the accumulation of the stilbenoid resveratrol in the cell membrane and cell wall during its production using Corynebacterium glutamicum and uncover the membrane rigidifying effect of this stilbenoid experimentally and with molecular dynamics simulations. A screen of free fatty acid supplements identifies palmitelaidic acid and linoleic acid as suitable additives to attenuate resveratrol’s cytotoxic effects resulting in a three-fold higher product titer. This cost-effective approach to counteract membrane-damaging effects of product accumulation is transferable to the microbial production of other polyphenols and may represent an engineering target for other membrane-active bioproducts

BacHBerry: BACterial Hosts for production of Bioactive phenolics from bERRY fruits

BACterial Hosts for production of Bioactive phenolics from bERRY fruits (BacHBerry) was a 3-year project funded by the Seventh Framework Programme (FP7) of the European Union that ran between November 2013 and October 2016. The overall aim of the project was to establish a sustainable and economically-feasible strategy for the production of novel high-value phenolic compounds isolated from berry fruits using bacterial platforms. The project aimed at covering all stages of the discovery and pre-commercialization process, including berry collection, screening and characterization of their bioactive components, identification and functional characterization of the corresponding biosynthetic pathways, and construction of Gram-positive bacterial cell factories producing phenolic compounds. Further activities included optimization of polyphenol extraction methods from bacterial cultures, scale-up of production by fermentation up to pilot scale, as well as societal and economic analyses of the processes. This review article summarizes some of the key findings obtained throughout the duration of the project