Terpenes and terpenoids are a group of isoprene-derived molecules that constitute the largest gro... more Terpenes and terpenoids are a group of isoprene-derived molecules that constitute the largest group of natural products and secondary metabolites produced by living things, with more than 25,000 compounds reported. These compounds are synthesized by enzymes called terpene synthases, which include several families of cyclases and enzymes. These are responsible for adding functional groups to cyclized structures. Fungal terpenoids are of great interest for their pharmacological properties; therefore, understanding the mechanisms that regulate their synthesis (regulation of the mevalonate pathway, regulation of gene expression, and availability of cofactors) is essential to direct their production. For this reason, this review addresses the detailed study of the biosynthesis of fungal terpenoids and their regulation by various physiological and environmental factors.
With the uncontrolled growth of multidrug-resistant bacteria, there is an urgent need to search f... more With the uncontrolled growth of multidrug-resistant bacteria, there is an urgent need to search for new therapeutic targets, to develop drugs with novel modes of bactericidal action. FoF1-ATP synthase plays a crucial role in bacterial bioenergetic processes, and it has emerged as an attractive antimicrobial target, validated by the pharmaceutical approval of an inhibitor to treat multidrug-resistant tuberculosis. In this work, we aimed to design, through two types of in silico strategies, new allosteric inhibitors of the ATP synthase, by targeting the catalytic β subunit, a centerpiece in communication between rotor subunits and catalytic sites, to drive the rotary mechanism. As a model system, we used the F1 sector of Escherichia coli, a bacterium included in the priority list of multidrug-resistant pathogens. Drug-like molecules and an IF1-derived peptide, designed through molecular dynamics simulations and sequence mining approaches, respectively, exhibited in vitro micromolar in...
The success of a Rhizobium sp. inoculant depends on a product with a high number of live bacteria... more The success of a Rhizobium sp. inoculant depends on a product with a high number of live bacteria that can nodulate a leguminous plant. Culture media and oxygen transfer were studied to improve the production of R. phaseoli in chemically defined and undefined media for scale-up from shake flasks to a pneumatic bioreactor. The effects of carbon and phosphate on R. phaseoli growth were evaluated, and the specific volumetric oxygen transfer coefficient (KLa) was determined in shake flasks and scale-up to bioreactors. Six-fold more viable biomass was obtained by increasing the phosphate concentration by 7.5-fold when using glucose. However, this increase was not observed when succinate was used. In the undefined medium, glucose induced a higher production of R. phaseoli in comparison with other carbon sources. The KLa of 6–11 h-1 produced a five-fold growth of biomass in shake-flask cultures. This KLa was used to produce a R. phaseoli-based inoculant in a bioreactor. The formation of ni...
SARS-CoV-2 is a novel β-coronavirus that caused the COVID-19 pandemic disease, which spread rapid... more SARS-CoV-2 is a novel β-coronavirus that caused the COVID-19 pandemic disease, which spread rapidly, infecting more than 134 million people, and killing almost 2.9 million thus far. Based on the urgent need for therapeutic and prophylactic strategies, the identification and characterization of antibodies has been accelerated, since they have been fundamental in treating other viral diseases. Here, we summarized in an integrative manner the present understanding of the immune response and physiopathology caused by SARS-CoV-2, including the activation of the humoral immune response in SARS-CoV-2 infection and therefore, the synthesis of antibodies. Furthermore, we also discussed about the antibodies that can be generated in COVID-19 convalescent sera and their associated clinical studies, including a detailed characterization of a variety of human antibodies and identification of antibodies from other sources, which have powerful neutralizing capacities. Accordingly, the development o...
The global rise in urbanization and industrial activity has led to the production and incorporati... more The global rise in urbanization and industrial activity has led to the production and incorporation of foreign contaminant molecules into ecosystems, distorting them and impacting human and animal health. Physical, chemical, and biological strategies have been adopted to eliminate these contaminants from water bodies under anthropogenic stress. Biotechnological processes involving microorganisms and enzymes have been used for this purpose; specifically, laccases, which are broad spectrum biocatalysts, have been used to degrade several compounds, such as those that can be found in the effluents from industries and hospitals. Laccases have shown high potential in the biotransformation of diverse pollutants using crude enzyme extracts or free enzymes. However, their application in bioremediation and water treatment at a large scale is limited by the complex composition and high salt concentration and pH values of contaminated media that affect protein stability, recovery and recycling....
Zoanthids of the genus Palythoa are distributed worldwide in shallow waters around coral reefs. L... more Zoanthids of the genus Palythoa are distributed worldwide in shallow waters around coral reefs. Like all cnidarians, they possess nematocysts that contain a large diversity of toxins that paralyze their prey. This work was aimed at isolating and functionally characterizing a cnidarian neurotoxic phospholipase named A2-PLTX-Pcb1a for the first time. This phospholipase was isolated from the venomous extract of the zoanthid Palythoa caribaeorum. This enzyme, which is Ca2+-dependent, is a 149 amino acid residue protein. The analysis of the A2-PLTX-Pcb1a sequence showed neurotoxic domain similitude with other neurotoxic sPLA2´s, but a different catalytic histidine domain. This is remarkable, since A2-PLTX-Pcb1a displays properties like those of other known PLA2 enzymes.
Understanding the structure, functionalities and biology of functional amyloids is an issue of em... more Understanding the structure, functionalities and biology of functional amyloids is an issue of emerging interest. Inclusion bodies, namely protein clusters formed in recombinant bacteria during protein production processes, have emerged as unanticipated, highly tunable models for the scrutiny of the physiology and architecture of functional amyloids. Based on an amyloidal skeleton combined with varying amounts of native or native-like protein forms, bacterial inclusion bodies exhibit an unusual arrangement that confers mechanical stability, biological activity and conditional protein release, being thus exploitable as versatile biomaterials. The applicability of inclusion bodies in biotechnology as enriched sources of protein and reusable catalysts, and in biomedicine as biocompatible topographies, nanopills, or mimetics of endocrine secretory granules has been largely validated. Beyond these uses, the dissection of how recombinant bacteria manage the aggregation of functional prote...
In the biopharmaceutical sector, Chinese hamster ovary (CHO) cells have become the host of choice... more In the biopharmaceutical sector, Chinese hamster ovary (CHO) cells have become the host of choice to produce recombinant proteins (r-proteins) due to their capacity for correct protein folding, assembly, and posttranslational modification. However, the production of therapeutic r-proteins in CHO cells is expensive and presents insufficient production yields for certain proteins. Effective culture strategies to increase productivity (qp) include a high glucose concentration in the medium and mild hypothermia (28-34 °C), but these changes lead to a reduced specific growth rate. To study the individual and combined impacts of glucose concentration, specific growth rate and mild hypothermia on culture performance and cell metabolism, we analyzed chemostat cultures of recombinant human tissue plasminogen activator (rh-tPA)-producing CHO cell lines fed with three glucose concentrations in feeding media (20, 30 and 40 mM), at two dilution rates (0.01 and 0.018 1/h) and two temperatures (33...
Terpenes and terpenoids are a group of isoprene-derived molecules that constitute the largest gro... more Terpenes and terpenoids are a group of isoprene-derived molecules that constitute the largest group of natural products and secondary metabolites produced by living things, with more than 25,000 compounds reported. These compounds are synthesized by enzymes called terpene synthases, which include several families of cyclases and enzymes. These are responsible for adding functional groups to cyclized structures. Fungal terpenoids are of great interest for their pharmacological properties; therefore, understanding the mechanisms that regulate their synthesis (regulation of the mevalonate pathway, regulation of gene expression, and availability of cofactors) is essential to direct their production. For this reason, this review addresses the detailed study of the biosynthesis of fungal terpenoids and their regulation by various physiological and environmental factors.
With the uncontrolled growth of multidrug-resistant bacteria, there is an urgent need to search f... more With the uncontrolled growth of multidrug-resistant bacteria, there is an urgent need to search for new therapeutic targets, to develop drugs with novel modes of bactericidal action. FoF1-ATP synthase plays a crucial role in bacterial bioenergetic processes, and it has emerged as an attractive antimicrobial target, validated by the pharmaceutical approval of an inhibitor to treat multidrug-resistant tuberculosis. In this work, we aimed to design, through two types of in silico strategies, new allosteric inhibitors of the ATP synthase, by targeting the catalytic β subunit, a centerpiece in communication between rotor subunits and catalytic sites, to drive the rotary mechanism. As a model system, we used the F1 sector of Escherichia coli, a bacterium included in the priority list of multidrug-resistant pathogens. Drug-like molecules and an IF1-derived peptide, designed through molecular dynamics simulations and sequence mining approaches, respectively, exhibited in vitro micromolar in...
The success of a Rhizobium sp. inoculant depends on a product with a high number of live bacteria... more The success of a Rhizobium sp. inoculant depends on a product with a high number of live bacteria that can nodulate a leguminous plant. Culture media and oxygen transfer were studied to improve the production of R. phaseoli in chemically defined and undefined media for scale-up from shake flasks to a pneumatic bioreactor. The effects of carbon and phosphate on R. phaseoli growth were evaluated, and the specific volumetric oxygen transfer coefficient (KLa) was determined in shake flasks and scale-up to bioreactors. Six-fold more viable biomass was obtained by increasing the phosphate concentration by 7.5-fold when using glucose. However, this increase was not observed when succinate was used. In the undefined medium, glucose induced a higher production of R. phaseoli in comparison with other carbon sources. The KLa of 6–11 h-1 produced a five-fold growth of biomass in shake-flask cultures. This KLa was used to produce a R. phaseoli-based inoculant in a bioreactor. The formation of ni...
SARS-CoV-2 is a novel β-coronavirus that caused the COVID-19 pandemic disease, which spread rapid... more SARS-CoV-2 is a novel β-coronavirus that caused the COVID-19 pandemic disease, which spread rapidly, infecting more than 134 million people, and killing almost 2.9 million thus far. Based on the urgent need for therapeutic and prophylactic strategies, the identification and characterization of antibodies has been accelerated, since they have been fundamental in treating other viral diseases. Here, we summarized in an integrative manner the present understanding of the immune response and physiopathology caused by SARS-CoV-2, including the activation of the humoral immune response in SARS-CoV-2 infection and therefore, the synthesis of antibodies. Furthermore, we also discussed about the antibodies that can be generated in COVID-19 convalescent sera and their associated clinical studies, including a detailed characterization of a variety of human antibodies and identification of antibodies from other sources, which have powerful neutralizing capacities. Accordingly, the development o...
The global rise in urbanization and industrial activity has led to the production and incorporati... more The global rise in urbanization and industrial activity has led to the production and incorporation of foreign contaminant molecules into ecosystems, distorting them and impacting human and animal health. Physical, chemical, and biological strategies have been adopted to eliminate these contaminants from water bodies under anthropogenic stress. Biotechnological processes involving microorganisms and enzymes have been used for this purpose; specifically, laccases, which are broad spectrum biocatalysts, have been used to degrade several compounds, such as those that can be found in the effluents from industries and hospitals. Laccases have shown high potential in the biotransformation of diverse pollutants using crude enzyme extracts or free enzymes. However, their application in bioremediation and water treatment at a large scale is limited by the complex composition and high salt concentration and pH values of contaminated media that affect protein stability, recovery and recycling....
Zoanthids of the genus Palythoa are distributed worldwide in shallow waters around coral reefs. L... more Zoanthids of the genus Palythoa are distributed worldwide in shallow waters around coral reefs. Like all cnidarians, they possess nematocysts that contain a large diversity of toxins that paralyze their prey. This work was aimed at isolating and functionally characterizing a cnidarian neurotoxic phospholipase named A2-PLTX-Pcb1a for the first time. This phospholipase was isolated from the venomous extract of the zoanthid Palythoa caribaeorum. This enzyme, which is Ca2+-dependent, is a 149 amino acid residue protein. The analysis of the A2-PLTX-Pcb1a sequence showed neurotoxic domain similitude with other neurotoxic sPLA2´s, but a different catalytic histidine domain. This is remarkable, since A2-PLTX-Pcb1a displays properties like those of other known PLA2 enzymes.
Understanding the structure, functionalities and biology of functional amyloids is an issue of em... more Understanding the structure, functionalities and biology of functional amyloids is an issue of emerging interest. Inclusion bodies, namely protein clusters formed in recombinant bacteria during protein production processes, have emerged as unanticipated, highly tunable models for the scrutiny of the physiology and architecture of functional amyloids. Based on an amyloidal skeleton combined with varying amounts of native or native-like protein forms, bacterial inclusion bodies exhibit an unusual arrangement that confers mechanical stability, biological activity and conditional protein release, being thus exploitable as versatile biomaterials. The applicability of inclusion bodies in biotechnology as enriched sources of protein and reusable catalysts, and in biomedicine as biocompatible topographies, nanopills, or mimetics of endocrine secretory granules has been largely validated. Beyond these uses, the dissection of how recombinant bacteria manage the aggregation of functional prote...
In the biopharmaceutical sector, Chinese hamster ovary (CHO) cells have become the host of choice... more In the biopharmaceutical sector, Chinese hamster ovary (CHO) cells have become the host of choice to produce recombinant proteins (r-proteins) due to their capacity for correct protein folding, assembly, and posttranslational modification. However, the production of therapeutic r-proteins in CHO cells is expensive and presents insufficient production yields for certain proteins. Effective culture strategies to increase productivity (qp) include a high glucose concentration in the medium and mild hypothermia (28-34 °C), but these changes lead to a reduced specific growth rate. To study the individual and combined impacts of glucose concentration, specific growth rate and mild hypothermia on culture performance and cell metabolism, we analyzed chemostat cultures of recombinant human tissue plasminogen activator (rh-tPA)-producing CHO cell lines fed with three glucose concentrations in feeding media (20, 30 and 40 mM), at two dilution rates (0.01 and 0.018 1/h) and two temperatures (33...
Uploads
Papers