Construction of Chemoenzymatic Linear Cascades for the Synthesis of Chiral Compounds

Inspired by nature, synthetic chemists try to mimic the efficient metabolic networks in living organisms to build complex molecules by combining different types of catalysts in the same reaction vessel. These multistep cascade processes provide many advantages to synthetic procedures, resulting in higher productivities with lower waste generation and cost. However, combining different chemo- and biocatalysts can be challenging as reaction conditions might differ greatly. As a highly multidisciplinary field that benefits from advances in chemical catalysis, molecular biology and reaction engineering, this area of study is rapidly progressing. In this Review, we highlight recent trends and advances in the construction of multistep chemoenzymatic one-pot cascades to access chiral compounds as well as the different strategies to solve current challenges in the field

New Trends and Future Opportunities in the Enzymatic Formation of C-C, C-N, and C-O bonds

Organic chemistry provides society with fundamental products we use daily. Concerns about the impact that the chemical industry has over the environment is propelling major changes in the way we manufacture chemicals. Biocatalysis offers an alternative to other synthetic approaches as it employs enzymes, Nature''s catalysts, to carry out chemical transformations. Enzymes are biodegradable, come from renewable sources, operate under mild reaction conditions, and display high selectivities in the processes they catalyse. As a highly multidisciplinary field, biocatalysis benefits from advances in different areas, and developments in the fields of molecular biology, bioinformatics, and chemical engineering have accelerated the extension of the range of available transformations (E. L. Bell et al., Nat. Rev. Meth. Prim. 2021, 1, 1–21). Recently, we surveyed advances in the expansion of the scope of biocatalysis via enzyme discovery and protein engineering (J. R. Marshall et al., Tetrahedron 2021, 82, 131926). Herein, we focus on novel enzymes currently available to the broad synthetic community for the construction of new C-C, C-N and C-O bonds, with the purpose of providing the non-specialist with new and alternative tools for chiral and sustainable chemical synthesis. © 2021 The Authors. ChemBioChem published by Wiley-VCH GmbH

Nomogram-based prediction of survival in patients with advanced oesophagogastric adenocarcinoma receiving first-line chemotherapy: a multicenter prospective study in the era of trastuzumab

Background: To develop and validate a nomogram and web-based calculator to predict overall survival (OS) in Caucasian-advanced oesophagogastric adenocarcinoma (AOA) patients undergoing first-line combination chemotherapy. Methods: Nine hundred twenty-four AOA patients treated at 28 Spanish teaching hospitals from January 2008 to September 2014 were used as derivation cohort. The result of an adjusted-Cox proportional hazards regression was represented as a nomogram and web-based calculator. The model was validated in 502 prospectively recruited patients treated between October 2014 and December 2016. Harrell's c-index was used to evaluate discrimination. Results: The nomogram includes seven predictors associated with OS: HER2-positive tumours treated with trastuzumab, Eastern Cooperative Oncology Group performance status, number of metastatic sites, bone metastases, ascites, histological grade, and neutrophil-to-lymphocyte ratio. Median OS was 5.8 (95% confidence interval (CI), 4.5–6.6), 9.4 (95% CI, 8.5–10.6), and 14 months (95% CI, 11.8–16) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the derivation set and 4.6 (95% CI, 3.3–8.1), 12.7 (95% CI, 11.3–14.3), and 18.3 months (95% CI, 14.6–24.2) for high-, intermediate-, and low-risk groups, respectively (P<0.001), in the validation set. The nomogram is well-calibrated and reveals acceptable discriminatory capacity, with optimism-corrected c-indices of 0.618 (95% CI, 0.591–0.631) and 0.673 (95% CI, 0.636–0.709) in derivation and validation groups, respectively. The AGAMENON nomogram outperformed the Royal Marsden Hospital (c-index=0.583; P=0.00046) and Japan Clinical Oncology Group prognostic indices (c-index=0.611; P=0.03351). Conclusions: We developed and validated a straightforward model to predict survival in Caucasian AOA patients initiating first-line polychemotherapy. This model can contribute to inform clinical decision-making and optimise clinical trial design

Metabolic alterations and distribution of five-carbon precursors in jasmonic acid-elicited Catharanthus roseus cell suspension cultures

Plant science

Sistema de evaluación institucional en enseñanza obligatoria en Iberoamérica

La presente aportación se focaliza, en este contexto, en la evaluación institucional externa (vinculada o no a la autoevaluación interna) y, por tanto, considera prioritariamente la manera como se evalúan los centros educativos como totalidad y no tanto alguno de sus aspectos (evaluación de la dirección, de los profesores, de los programas, etc.), que también pueden estar considerados. El énfasis también está en conocer la organización y desarrollo del sistema de evaluación. Recoge la visión de 43 especialistas de trece países iberoamericanos sobre las formas de entender y promover la evaluación institucional en sus centros educativos. Sus aportaciones, que deben contextualizarse en las particularidades educativas de sus países (ya presentadas en anteriores informes de la RedAGE), presentan los aspectos generales y normativos de la evaluación, las formas cómo se organiza, los efectos institucionales que tienen y algunas reflexiones, retos y propuestas para la mejora. Su orientación es claramente práctica y se vincula al encuentro anual que la RedAGE realizado los días 16 y 17 de mayo de 2016 en la ciudad de Leiria (Portugal). Allí, los representantes de las organizaciones miembro seleccionaron la temática por su interés actual (con clara vinculación a la mejora de los sistemas educativos y la acreditación institucional), consensuaron la estructura de las aportaciones y realizaron un intercambio de posibles ideas sobre la temática. Se cubre así y como en ocasiones anteriores el propósito fundamental de la RedAGE, como es el de fomentar el intercambio de experiencias, la promoción del conocimiento sobre administración y gestión educativa y la reflexión sobre la práctica de la gestión. La finalidad última sigue siendo la de mejorar el funcionamiento de los centros educativos (y, a través de ellos, de los sistemas educativos), procurando sean de calidad y un instrumento para el cambio profesional y social

Application of engineered biocatalysts for the synthesis of active pharmaceutical ingredients (APIs)

Genetic engineering of enzymes has played a significant role in multiple pharmaceutical synthetic processes. The need for selective, robust catalysts that can operate under process chemistry conditions has driven the need for mutagenesis approaches, which have successfully delivered a variety of process-optimized biocatalysts. In this chapter we give an overview of different directed evolution methods that have been applied to pharmaceutical intermediates during the last decade. The exciting progress that has been made since the landmark sitagliptin study in 2010 demonstrates the role that engineered biocatalysts can play in the manufacture of active pharmaceutical ingredients (APIs).Peer reviewe

New trends and future opportunities in the enzymatic formation of C−C, C−N, and C−O bonds

Organic chemistry provides society with fundamental products we use daily. Concerns about the impact that the chemical industry has over the environment is propelling major changes in the way we manufacture chemicals. Biocatalysis offers an alternative to other synthetic approaches as it employs enzymes, Nature's catalysts, to carry out chemical transformations. Enzymes are biodegradable, come from renewable sources, operate under mild reaction conditions, and display high selectivities in the processes they catalyse. As a highly multidisciplinary field, biocatalysis benefits from advances in different areas, and developments in the fields of molecular biology, bioinformatics, and chemical engineering have accelerated the extension of the range of available transformations (E. L. Bell et al., Nat. Rev. Meth. Prim. 2021, 1, 1–21). Recently, we surveyed advances in the expansion of the scope of biocatalysis via enzyme discovery and protein engineering (J. R. Marshall et al., Tetrahedron 2021, 82, 131926). Herein, we focus on novel enzymes currently available to the broad synthetic community for the construction of new C−C, C−N and C−O bonds, with the purpose of providing the non-specialist with new and alternative tools for chiral and sustainable chemical synthesis.We would like to thank the Industrial Biotechnology Innovation Centre (IBioIC) and Biotechnology and Biological Sciences Research Council (BBSRC) for the awarding the CASE studentship to J.R.M. from Prozomix Ltd. J.J.S. is grateful to the Industrial Affiliates of CoEBio3 for a PhD studentship. N.J.T. is grateful to the ERC for the award of an Advanced Grant (Grant number 742987). J.M.-S. thanks the ARAID Foundation for personal funding and the Research Group E07_20R for scientific support. He also thanks the Agencia Estatal de Investigación for financial support (PID2020-113351RA-100/AEI/10.13039/501100011033).Peer reviewe