Contributions of Latin American researchers in the understanding of the novel coronavirus outbreak: a literature review.

This article aimed to give the visibility of Latin American researchers' contributions to the comprehension of COVID-19; our method was a literature review. Currently, the world is facing a health and socioeconomic crisis caused by the novel coronavirus, SARS-CoV-2, and its disease COVID-19. Therefore, in less than 4 months, researchers have published a significant number of articles related to this novel virus. For instance, a search focused on the Scopus database on 10 April 2020, showed 1,224 documents published by authors with 1,797 affiliations from 80 countries. A total of 25.4%, 24.0% and 12.6% of these national affiliations were from China, Europe and the USA, respectively, making these regions leaders in COVID-19 research. In the case of Latin America, on 10 April 2020, we searched different databases, such as Scopus, PubMed and Web of Science, finding that the contribution of this region was 2.7 ± 0.6% of the total publications found. In other words, we found 153 publications related to COVID-19 with at least one Latin American researcher. We summarized and processed the information from these 153 publications, finding active participation in topics like medical, social and environmental considerations, bioinformatics and epidemiology.

Clostridium butyricum population balance model: Predicting dynamic metabolic flux distributions using an objective function related to extracellular glycerol content.

BACKGROUND: Extensive experimentation has been conducted to increment 1,3-propanediol (PDO) production using Clostridium butyricum cultures in glycerol, but computational predictions are limited. Previously, we reconstructed the genome-scale metabolic (GSM) model iCbu641, the first such model of a PDO-producing Clostridium strain, which was validated at steady state using flux balance analysis (FBA). However, the prediction ability of FBA is limited for batch and fed-batch cultures, which are the most often employed industrial processes. RESULTS: We used the iCbu641 GSM model to develop a dynamic flux balance analysis (DFBA) approach to predict the PDO production of the Colombian strain Clostridium sp IBUN 158B. First, we compared the predictions of the dynamic optimization approach (DOA), static optimization approach (SOA), and direct approach (DA). We found no differences between approaches, but the DOA simulation duration was nearly 5000 times that of the SOA and DA simulations. Experimental results at glycerol limitation and glycerol excess allowed for validating dynamic predictions of growth, glycerol consumption, and PDO formation. These results indicated a 4.4% error in PDO prediction and therefore validated the previously proposed objective functions. We performed two global sensitivity analyses, finding that the kinetic input parameters of glycerol uptake flux had the most significant effect on PDO predictions. The other input parameters evaluated during global sensitivity analysis were biomass composition (precursors and macromolecules), death constants, and the kinetic parameters of acetic acid secretion flux. These last input parameters, all obtained from other Clostridium butyricum cultures, were used to develop a population balance model (PBM). Finally, we simulated fed-batch cultures, predicting a final PDO production near to 66 g/L, almost three times the PDO predicted in the best batch culture. CONCLUSIONS: We developed and validated a dynamic approach to predict PDO production using the iCbu641 GSM model and the previously proposed objective functions. This validated approach was used to propose a population model and then an increment in predictions of PDO production through fed-batch cultures. Therefore, this dynamic model could predict different scenarios, including its integration into downstream processes to predict technical-economic feasibilities and reducing the time and costs associated with experimentation.

Development of a Chlamydomonas reinhardtii metabolic network dynamic model to describe distinct phenotypes occurring at different CO2 levels.

The increase in atmospheric CO2 due to anthropogenic activities is generating climate change, which has resulted in a subsequent rise in global temperatures with severe environmental impacts. Biological mitigation has been considered as an alternative for environmental remediation and reduction of greenhouse gases in the atmosphere. In fact, the use of easily adapted photosynthetic organisms able to fix CO2 with low-cost operation is revealing its high potential for industry. Among those organism, the algae Chlamydomonas reinhardtii have gain special attention as a model organism for studying CO2 fixation, biomass accumulation and bioenergy production upon exposure to several environmental conditions. In the present study, we studied the Chlamydomonas response to different CO2 levels by comparing metabolomics and transcriptomics data with the predicted results from our new-improved genomic-scale metabolic model. For this, we used in silico methods at steady dynamic state varying the levels of CO2. Our main goal was to improve our capacity for predicting metabolic routes involved in biomass accumulation. The improved genomic-scale metabolic model presented in this study was shown to be phenotypically accurate, predictive, and a significant improvement over previously reported models. Our model consists of 3726 reactions and 2436 metabolites, and lacks any thermodynamically infeasible cycles. It was shown to be highly sensitive to environmental changes under both steady-state and dynamic conditions. As additional constraints, our dynamic model involved kinetic parameters associated with substrate consumption at different growth conditions (i.e., low CO2-heterotrophic and high CO2-mixotrophic). Our results suggest that cells growing at high CO2 (i.e., photoautotrophic and mixotrophic conditions) have an increased capability for biomass production. In addition, we have observed that ATP production also seems to be an important limiting factor for growth under the conditions tested. Our experimental data (metabolomics and transcriptomics) and the results predicted by our model clearly suggest a differential behavior between low CO2-heterotrophic and high CO2-mixotrophic growth conditions. The data presented in the current study contributes to better dissect the biological response of C. reinhardtii, as a dynamic entity, to environmental and genetic changes. These findings are of great interest given the biotechnological potential of this microalga for CO2 fixation, biomass accumulation, and bioenergy production.

Clostridium butyricum maximizes growth while minimizing enzyme usage and ATP production: metabolic flux distribution of a strain cultured in glycerol.

BACKGROUND: The increase in glycerol obtained as a byproduct of biodiesel has encouraged the production of new industrial products, such as 1,3-propanediol (PDO), using biotechnological transformation via bacteria like Clostridium butyricum. However, despite the increasing role of Clostridium butyricum as a bio-production platform, its metabolism remains poorly modeled. RESULTS: We reconstructed iCbu641, the first genome-scale metabolic (GSM) model of a PDO producer Clostridium strain, which included 641 genes, 365 enzymes, 891 reactions, and 701 metabolites. We found an enzyme expression prediction of nearly 84% after comparison of proteomic data with flux distribution estimation using flux balance analysis (FBA). The remaining 16% corresponded to enzymes directionally coupled to growth, according to flux coupling findings (FCF). The fermentation data validation also revealed different phenotype states that depended on culture media conditions; for example, Clostridium maximizes its biomass yield per enzyme usage under glycerol limitation. By contrast, under glycerol excess conditions, Clostridium grows sub-optimally, maximizing biomass yield while minimizing both enzyme usage and ATP production. We further evaluated perturbations in the GSM model through enzyme deletions and variations in biomass composition. The GSM predictions showed no significant increase in PDO production, suggesting a robustness to perturbations in the GSM model. We used the experimental results to predict that co-fermentation was a better alternative than iCbu641 perturbations for improving PDO yields. CONCLUSIONS: The agreement between the predicted and experimental values allows the use of the GSM model constructed for the PDO-producing Clostridium strain to propose new scenarios for PDO production, such as dynamic simulations, thereby reducing the time and costs associated with experimentation.