Integrated, systems metabolic picture of acetone-butanol-ethanol fermentation by Clostridium acetobutylicum.

Microbial metabolism involves complex, system-level processes implemented via the orchestration of metabolic reactions, gene regulation, and environmental cues. One canonical example of such processes is acetone-butanol-ethanol (ABE) fermentation by Clostridium acetobutylicum, during which cells convert carbon sources to organic acids that are later reassimilated to produce solvents as a strategy for cellular survival. The complexity and systems nature of the process have been largely underappreciated, rendering challenges in understanding and optimizing solvent production. Here, we present a system-level computational framework for ABE fermentation that combines metabolic reactions, gene regulation, and environmental cues. We developed the framework by decomposing the entire system into three modules, building each module separately, and then assembling them back into an integrated system. During the model construction, a bottom-up approach was used to link molecular events at the single-cell level into the events at the population level. The integrated model was able to successfully reproduce ABE fermentations of the WT C. acetobutylicum (ATCC 824), as well as its mutants, using data obtained from our own experiments and from literature. Furthermore, the model confers successful predictions of the fermentations with various network perturbations across metabolic, genetic, and environmental aspects. From foundation to applications, the framework advances our understanding of complex clostridial metabolism and physiology and also facilitates the development of systems engineering strategies for the production of advanced biofuels.

Extinction, coexistence, and localized patterns of a bacterial population with contact-dependent inhibition.

BACKGROUND: Contact-dependent inhibition (CDI) has been recently revealed as an intriguing but ubiquitous mechanism for bacterial competition in which a species injects toxins into its competitors through direct physical contact for growth suppression. Although the molecular and genetic aspects of CDI systems are being increasingly explored, a quantitative and systematic picture of how CDI systems benefit population competition and hence alter corresponding competition outcomes is not well elucidated. RESULTS: By constructing a mathematical model for a population consisting of CDI+ and CDI- species, we have systematically investigated the dynamics and possible outcomes of population competition. In the well-mixed case, we found that the two species are mutually exclusive: Competition always results in extinction for one of the two species, with the winner determined by the tradeoff between the competitive benefit of the CDI+ species and its growth disadvantage from increased metabolic burden. Initial conditions in certain circumstances can also alter the outcome of competition. In the spatial case, in addition to exclusive extinction, coexistence and localized patterns may emerge from population competition. For spatial coexistence, population diffusion is also important in influencing the outcome. Using a set of illustrative examples, we further showed that our results hold true when the competition of the population is extended from one to two dimensional space. CONCLUSIONS: We have revealed that the competition of a population with CDI can produce diverse patterns, including extinction, coexistence, and localized aggregation. The emergence, relative abundance, and characteristic features of these patterns are collectively determined by the competitive benefit of CDI and its growth disadvantage for a given rate of population diffusion. Thus, this study provides a systematic and statistical view of CDI-based bacterial population competition, expanding the spectrum of our knowledge about CDI systems and possibly facilitating new experimental tests for a deeper understanding of bacterial interactions.

Ghrelin in plants: what is the function of an appetite hormone in plants?

In the present work, we provide compelling evidence for the expression of a ghrelin-like peptide hormone that has only been associated with animals, in various plant tissues. Ghrelin, the appetite stimulating hormone, has been identified from a number of different species including humans, rat, pig, mouse, gerbil, eel, goldfish, bullfrog and chicken. The study here was conducted using an immunohistochemistry assay to screen whether plants have any ghrelin immunoreactivity. In this respect, Prunus x domestica L. and Marus alba were examined. Immunohistochemistry results showed that there is a strong human ghrelin immunoreactivity substance in the parenchyma cells of these plants. This was entirely unexpected since this hormone was considered to be present solely in animals. Thus, this study is the first to report the presence of a peptide with ghrelin-like activity in plants, a finding that has only been observed in the animal kingdom. RIA analysis confirmed that these plants contain significant amounts of this substance. Furthermore, reverse-phase HPLC analyses of plant extracts showed an elution characteristic of the peptide identical to that of human ghrelin. In general, fruit from both plants had higher levels of the peptide than the vegetative parts.

[Comparative analysis at the nucleotide level of the genes encoding the lactate dehydrogenase enzyme of Plasmodium vivax and Plasmodium falciparum.]. / Plasmodium vivax ve Plasmodium falciparum'un laktat dehidrogenaz enzimini kodlayan genlerinin nükleotid düzeyinde karsilastirmali analizi.

In this study, the nucleotide sequence of the enzyme lactate dehydrogenase from Plasmodium vivax has been compared to the same enzyme from another malaria parasite Plasmodium falciparum. It was found that the identity between two sequences was 74.8%. The percentage of the GC value was found to be higher in the Plasmodium vivax lactate dehydrogenase (46.6%) than in that of Plasmodium falciparum (33%). The nucleotide sequence that corresponds to the 5 amino acid insertion in Plasmodium lactate dehydrogenase is also present in Plasmodium vivax. This site will be targeted in the design of novel antimalarials for Plasmodium vivax as has been for Plasmodium falciparum.

Cloning, sequence and expression of the lactate dehydrogenase gene from the human malaria parasite, Plasmodium vivax.

Increased drug resistance to anti-malarials highlights the need for the development of new therapeutics for the treatment of malaria. To this end, the lactate dehydrogenase (LDH) gene was cloned and sequenced from genomic DNA of Plasmodium vivax ( PvLDH) Belem strain. The 316 amino acid protein-coding region of the PvLDH gene was inserted into the prokaryotic expression vector pKK223-3 and a 34 kDa protein with LDH activity was expressed in E. coli. Structural differences between human LDHs and PfLDH make the latter an attractive target for inhibitors leading to novel anti-malarial drugs. The sequence similarity between PvLDH and PfLDH (90% residue identity and no insertions or deletions) indicate that the same approach could be applied to Plasmodium vivax, the most common human malaria parasite in the world.