Biocatalysis as Useful Tool in Asymmetric Synthesis: An Assessment of Recently Granted Patents (2014–2019)

The broad interdisciplinary nature of biocatalysis fosters innovation, as different technical fields are interconnected and synergized. A way to depict that innovation is by conducting a survey on patent activities. This paper analyses the intellectual property activities of the last five years (2014–2019) with a specific focus on biocatalysis applied to asymmetric synthesis. Furthermore, to reflect the inventive and innovative steps, only patents that were granted during that period are considered. Patent searches using several keywords (e.g., enzyme names) have been conducted by using several patent engine servers (e.g., Espacenet, SciFinder, Google Patents), with focus on granted patents during the period 2014–2019. Around 200 granted patents have been identified, covering all enzyme types. The inventive pattern focuses on the protection of novel protein sequences, as well as on new substrates. In some other cases, combined processes, multi-step enzymatic reactions, as well as process conditions are the innovative basis. Both industries and academic groups are active in patenting. As a conclusion of this survey, we can assert that biocatalysis is increasingly recognized as a useful tool for asymmetric synthesis and being considered as an innovative option to build IP and protect synthetic routes

Recent developments in the synthesis of β-diketones

Apart from being one of the most important intermediates in chemical synthesis, broadly used in the formation of C–C bonds among other processes, the β-dicarbonyl structure is present in a huge number of biologically and pharmaceutically active compounds. In fact, mainly derived from the well-known antioxidant capability associated with the corresponding enol tautomer, β-diketones are valuable compounds in the treatment of many pathological disorders, such as cardiovascular and liver diseases, hypertension, obesity, diabetes, neurological disorders, inflammation, skin dis-eases, fibrosis, or arthritis; therefore, the synthesis of these structures is an area of overwhelming interest for organic chemists. This paper is devoted to the advances achieved in the last ten years for the preparation of 1,3-diketones, using different chemical (Claisen, hydration of alkynones, decar-boxylative coupling) or catalytic (biocatalysis, organocatalytic, metal-based catalysis) methodologies: Additionally, the preparation of branched β-dicarbonyl compounds by means of α-functionalization of non-substituted 1,3-diketones are also discussed

Multienzymatic processes involving baeyer–villiger monooxygenases

Baeyer–Villiger monooxygenases (BVMOs) are flavin-dependent oxidative enzymes capable of catalyzing the insertion of an oxygen atom between a carbonylic Csp2 and the Csp3 at the alpha position, therefore transforming linear and cyclic ketones into esters and lactones. These enzymes are dependent on nicotinamides (NAD(P)H) for the flavin reduction and subsequent reaction with molecular oxygen. BVMOs can be included in cascade reactions, coupled to other redox enzymes, such as alcohol dehydrogenases (ADHs) or ene-reductases (EREDs), so that the direct conversion of alcohols or α,β-unsaturated carbonylic compounds to the corresponding esters can be achieved. In the present review, the different synthetic methodologies that have been performed by employing multienzymatic strategies with BVMOs combining whole cells or isolated enzymes, through sequential or parallel methods, are described, with the aim of highlighting the advantages of performing multienzymatic systems, and show the recent advances for overcoming the drawbacks of using BVMOs in these techniques.Ministerio de Ciencia e Innovación PID2019-105337RB-C22Banco Santander-UCM PR87/19-2267

Magnetic micro-macro biocatalysts applied to industrial bioprocesses

The use of magnetic biocatalysts is highly beneficial in bioprocesses technology, as it allows their easy recovering and enhances biocatalyst lifetime. Thus, it simplifies operational processing and increases efficiency, leading to more cost-effective processes. The use of small-size matrices as carriers for enzyme immobilization enables to maximize surface area and catalysts loading, also reducing diffusion limitations. As highly expensive nanoparticles (nm size) usually aggregate, their application at large scale is not recommended. In contrast, the use of magnetic micro-macro (µm-mm size) matrices leads to more homogeneous biocatalysts with null or very low aggregation, which facilitates an easy handling and recovery. The present review aims to highlight recent trends in the application of medium-to-high size magnetic biocatalysts in different areas (biodiesel production, food and pharma industries, protein purification or removal of environmental contaminants). The advantages and disadvantages of these above-mentioned magnetic biocatalysts in bioproces

Utilización de hidrolasas en la preparación de fármacos e intermedios homoquirales

The excellent regio and steroselectivity of biocatalysts, combined with their environmental friendly behaviour, make possible to carry out under biocatalytical conditions many processes which, conducted on strictly classical methodologies, would demand expensive and tedious protection and de-protection steps. In this work we review some examples in which hydrolases (the most useful enzymes in the Biotransformations field) catalyse different reactions for synthesizing only the therapeutically essential stereoisomer of different homochiral building blocks for drugs. Thus, processes leading to antiviral, anticancer, antihypertensive or antiinflammatory drugs, along with many others, are described, remarking the versatility and utility of the biocatalysts in the above-mentioned processesLa exquisita regio y estereoselectividad que presentan los biocatalizadores, amén de la buena sostenibilidad inherente a su empleo, permiten la realización de protocolos sintéticos difícilmente alcanzables por las metodologías clásicas, a menos que se lleven a cabo costosos procesos de protección y desprotección. En este trabajo se revisan algunos ejemplos en los cuales las hidrolasas (las enzimas más empleadas dentro del ámbito de las Biotransformaciones) están implicadas como biocatalizadores para la obtención del eutómero (esteroisómero activo, que presenta la actividad terapéutica deseada) bien de diferentes fármacos quirales o bien de precursores a través de los cuales se puedan sintetizar. Así, se comentarán distintos tipos de Biotransformaciones para la obtención de compuestos con diferentes actividades: antivirales, anticancerosos, antihipertensivos, antiinflamatorios, etc, haciendo hincapié en la versatilidad y comodidad del empleo de los biocatalizadores en los pasos sintéticos descritos

One Pot Use of Combilipases for Full Modification of Oils and Fats: Multifunctional and Heterogeneous Substrates

Lipases are among the most utilized enzymes in biocatalysis. In many instances, the main reason for their use is their high specificity or selectivity. However, when full modification of a multifunctional and heterogeneous substrate is pursued, enzyme selectivity and specificity become a problem. This is the case of hydrolysis of oils and fats to produce free fatty acids or their alcoholysis to produce biodiesel, which can be considered cascade reactions. In these cases, to the original heterogeneity of the substrate, the presence of intermediate products, such as diglycerides or monoglycerides, can be an additional drawback. Using these heterogeneous substrates, enzyme specificity can promote that some substrates (initial substrates or intermediate products) may not be recognized as such (in the worst case scenario they may be acting as inhibitors) by the enzyme, causing yields and reaction rates to drop. To solve this situation, a mixture of lipases with different specificity, selectivity and differently affected by the reaction conditions can offer much better results than the use of a single lipase exhibiting a very high initial activity or even the best global reaction course. This mixture of lipases from different sources has been called “combilipases” and is becoming increasingly popular. They include the use of liquid lipase formulations or immobilized lipases. In some instances, the lipases have been coimmobilized. Some discussion is offered regarding the problems that this coimmobilization may give rise to, and some strategies to solve some of these problems are proposed. The use of combilipases in the future may be extended to other processes and enzymes.This research was funded by Ministerio de Ciencia e Innovación-Spanish Government (project number CTQ2017-86170-R) and Generalitat Valenciana (PROMETEO/2018/076)

Enzyme production of d-gluconic acid and glucose oxidase: successful tales of cascade reactions

This review mainly focuses on the use of glucose oxidase in the production of D-gluconic acid, which is a reactant of undoubtable interest in different industrial areas. The enzyme has been used in numerous instances as a model reaction to study the problems of oxygen supply in bioreactors. One of the main topics in this review is the problem of the generated side product, hydrogen peroxide, as it is an enzyme-inactivating reagent. Different ways to remove hydrogen peroxide have been used, such as metal catalysts and use of whole cells; however, the preferred method is the coupling glucose oxidase with catalase. The different possibilities of combining these enzymes have been discussed (use of free enzymes, independently immobilized enzymes or co-immobilized enzymes). Curiously, some studies propose the addition of hydrogen peroxide to this co-immobilized enzyme system to produce oxygen in situ. Other cascade reactions directed toward the production of gluconic acid from polymeric substrates will be presented; these will mainly involve the transformation of polysaccharides (amylases, cellulases, etc.) but will not be limited to those (e.g., gluconolactonase). In fact, glucose oxidase is perhaps one of most successful enzymes, and it is involved in a wide range of cascade reactions. Finally, other applications of the enzyme have been reviewed, always based on the production of D-gluconic acid, which produces a decrease in the pH, a decrease in the oxygen availability or the production of hydrogen peroxide; in many instances, cascade reactions are also utilized. Thus, this review presents many different cascade reactions and discusses the advantages/drawbacks of the use of co-immobilized enzymes.We gratefully recognize the financial support from Ministerio de Ciencia e Innovación-Spanish Government and FEDER funds (project number CTQ2017-86170-R, RTI2018-095291-BI00, MAT2017-87579-R) and Generalitat Valenciana (PROMETEO/2018/076). DC thank to Ministerio de Ciencia e Innovacion-Spanish Government by a FPI. PWT thanks to the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001

甘味受容体における呈味調節物質作用モデルの構築及びその検証

学位の種別: 課程博士審査委員会委員 : (主査)東京大学准教授 三坂 巧, 東京大学教授 伏信 進矢, 東京大学特任教授 朝倉 富子, 東京大学准教授 永田 宏次, 東京大学准教授 寺田 透University of Tokyo(東京大学

Perspectivas de la empresa y la economía mexicana frente a la reestructuración productiva

1 archivo PDF (404 páginas)Este texto se presenta una reflexión de investigadores de la UAM, así como de otras Instituciones de Educación Superior respecto al marco en el que se han desenvuelto las empresas mexicanas en los últimos años, así como del desarrollo en algunos de sus sistemas organizacionales. PALABRAS CLAVE: Mexico Economic policy 1970-1994