40 research outputs found
Fermentative production of isobutene
Isobutene (2-methylpropene) is one of those chemicals for which bio-based production might replace the petrochemical production in the future. Currently, more than 10 million metric tons of isobutene are produced on a yearly basis. Even though bio-based production might also be achieved through chemocatalytic or thermochemical methods, this review focuses on fermentative routes from sugars. Although biological isobutene formation is known since the 1970s, extensive metabolic engineering is required to achieve economically viable yields and productivities. Two recent metabolic engineering developments may enable anaerobic production close to the theoretical stoichiometry of 1isobutene + 2CO2 + 2H2O per mol of glucose. One relies on the conversion of 3-hydroxyisovalerate to isobutene as a side activity of mevalonate diphosphate decarboxylase and the other on isobutanol dehydration as a side activity of engineered oleate hydratase. The latter resembles the fermentative production of isobutanol followed by isobutanol recovery and chemocatalytic dehydration. The advantage of a completely biological route is that not isobutanol, but instead gaseous isobutene is recovered from the fermenter together with CO2. The low aqueous solubility of isobutene might also minimize product toxicity to the microorganisms. Although developments are at their infancy, the potential of a large scale fermentative isobutene production process is assessed. The production costs estimate is 0.9 € kg−1, which is reasonably competitive. About 70% of the production costs will be due to the costs of lignocellulose hydrolysate, which seems to be a preferred feedstock
Fumaric acid production by fermentation
The potential of fumaric acid as a raw material in the polymer industry and the increment of cost of petroleum-based fumaric acid raises interest in fermentation processes for production of this compound from renewable resources. Although the chemical process yields 112% w/w fumaric acid from maleic anhydride and the fermentation process yields only 85% w/w from glucose, the latter raw material is three times cheaper. Besides, the fermentation fixes CO2. Production of fumaric acid by Rhizopus species and the involved metabolic pathways are reviewed. Submerged fermentation systems coupled with product recovery techniques seem to have achieved economically attractive yields and productivities. Future prospects for improvement of fumaric acid production include metabolic engineering approaches to achieve low pH fermentations
An overview of the recent developments on fructooligosaccharide production and applications
Over the past years, many researchers have suggested
that deficiencies in the diet can lead to disease states
and that some diseases can be avoided through an adequate
intake of relevant dietary components. Recently, a great interest
in dietary modulation of the human gut has been registered.
Prebiotics, such as fructooligosaccharides (FOS), play a key
role in the improvement of gut microbiota balance and in
individual health. FOS are generally used as components of
functional foods, are generally regarded as safe (generally
recognized as safe status—from the Food and Drug Administration,
USA), and worth about 150€ per kilogram. Due to
their nutrition- and health-relevant properties, such as moderate
sweetness, low carcinogenicity, low calorimetric value,
and low glycemic index, FOS have been increasingly used
by the food industry. Conventionally, FOS are produced
through a two-stage process that requires an enzyme production
and purification step in order to proceed with the chemical
reaction itself. Several studies have been conducted on the
production of FOS, aiming its optimization toward the development
of more efficient production processes and their potential
as food ingredients. The improvement of FOS yield and
productivity can be achieved by the use of different fermentative
methods and different microbial sources of FOS producing
enzymes and the optimization of nutritional and
culture parameter; therefore, this review focuses on the latest
progresses in FOS research such as its production, functional
properties, and market data.Agencia de Inovacao (AdI)-Project BIOLIFE reference PRIME 03/347. Ana Dominguez acknowledges Fundacao para a Ciencia e a Tecnologia, Portugal, for her PhD grant reference SFRH/BD/23083/2005
Emerging concepts in biomarker discovery; The US-Japan workshop on immunological molecular markers in oncology
Supported by the Office of International Affairs, National Cancer Institute (NCI), the "US-Japan Workshop on Immunological Biomarkers in Oncology" was held in March 2009. The workshop was related to a task force launched by the International Society for the Biological Therapy of Cancer (iSBTc) and the United States Food and Drug Administration (FDA) to identify strategies for biomarker discovery and validation in the field of biotherapy. The effort will culminate on October 28th 2009 in the "iSBTc-FDA-NCI Workshop on Prognostic and Predictive Immunologic Biomarkers in Cancer", which will be held in Washington DC in association with the Annual Meeting. The purposes of the US-Japan workshop were a) to discuss novel approaches to enhance the discovery of predictive and/or prognostic markers in cancer immunotherapy; b) to define the state of the science in biomarker discovery and validation. The participation of Japanese and US scientists provided the opportunity to identify shared or discordant themes across the distinct immune genetic background and the diverse prevalence of disease between the two Nations
Electroacupuncture to treat gastroesophageal reflux disease: study protocol for a randomized controlled trial
Photochemical transformations accelerated in continuous-flow reactors: basic concepts and applications
Continuous-flow photochemistry is used increasingly by researchers in academia and industry to facilitate photochemical processes and their subsequent scale-up. However, without detailed knowledge concerning the engineering aspects of photochemistry, it can be quite challenging to develop a suitable photochemical microreactor for a given reaction. In this review, we provide an up-to-date overview of both technological and chemical aspects associated with photochemical processes in microreactors. Important design considerations, such as light sources, material selection, and solvent constraints are discussed. In addition, a detailed description of photon and mass-transfer phenomena in microreactors is made and fundamental principles are deduced for making a judicious choice for a suitable photomicroreactor. The advantages of microreactor technology for photochemistry are described for UV and visible-light driven photochemical processes and are compared with their batch counterparts. In addition, different scale-up strategies and limitations of continuous-flow microreactors are discussed
A mild and fast photocatalytic trifluoromethylation of thiols in batch and continuous-flow
S-CF3 bonds are important structural motifs in various pharmaceutical and agrochemical compounds. However, their preparation remains a major challenge in synthetic organic chemistry. Here, we report the development of a mild and fast photocatalytic trifluoromethylation of thiols. The combination of commercially available Ru(bpy)(3)Cl-2, visible light and inexpensive CF3I gas proved to be an efficient method for the direct trifluoromethylation of thiols. The protocol is demonstrated on a wide range of aromatic, hetero-aromatic and aliphatic substrates in both batch and continuous microflow (32 examples, 52-98% yield). Process intensification through continuous microflow application resulted in a 15-fold increase in production rate (0.25 mmol min(-1)) due to improved gas-liquid mass transfer, enhanced irradiation as well as convenient handling of the gaseous CF3 source. Furthermore, the efficiency of the flow process allowed to reduce the amount of CF3I (1.1 equivalent) to reach full conversion
Metal-free photocatalytic aerobic oxidation of thiols to disulfides in batch and continuous-flow
Disulfides represent significant molecular and structural features in various biologically active compounds and fine chemicals. Therefore, the development of mild, efficient and sustainable methods to access disulfides is of great importance. Here, we describe the development of a mild metal-free photocatalytic aerobic oxidation of thiols to disulfides using Eosin Y and visible-light irradiation. A continuous flow procedure was developed to accelerate the photocatalytic process, enabling the preparation of disulfides with high purity in a time-frame of minutes. The mildness and applicability of our method was exemplified by the flow synthesis of the cyclic peptide hormone, oxytocin, requiring only a 200 s reaction time and an efficient one-pot batch protocol for the preparation of the therapeutic thiuram disulfide, disulfiram
Late-stage difluoromethylation: concepts, developments and perspective
This review describes the recent advances made in difluoromethylation processes based on X–CF2H bond formation where X is C(sp), C(sp2), C(sp3), O, N or S, a field of research that has benefited from the invention of multiple difluoromethylation reagents. The last decade has witnessed an upsurge of metal-based methods that can transfer CF2H to C(sp2) sites both in stoichiometric and catalytic mode. Difluoromethylation of C(sp2)–H bond has also been accomplished through Minisci-type radical chemistry, a strategy best applied to heteroaromatics. Examples of electrophilic, nucleophilic, radical and cross-coupling methods have appeared to construct C(sp3)–CF2H bonds, but cases of stereoselective difluoromethylation are still limited. In this sub-field, an exciting departure is the precise site-selective installation of CF2H onto large biomolecules such as proteins. The formation of X–CF2H bond where X is oxygen, nitrogen or sulfur is conventionally achieved upon reaction with ClCF2H; more recently, numerous protocols have achieved X–H insertion with novel non-ozone depleting difluorocarbene reagents. All together, these advances have streamlined access to molecules of pharmaceutical relevance, and generated interest for process chemistry