Positive feedback exists and drives the glucose-mediated repression in Escherichia coli

Aggarwal, Ritesh Kumar; Narang, Atul

doi:10.1016/j.bpj.2022.01.017

Cited by 3 publications

(1 citation statement)

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“…Begins when the glucose supply runs out, and growth ceases. During the first stage of the transition, three things happen that will ultimately result in the de-repression of the lac operon: 1) the dilution caused by growth stops, 2) the inhibition of lac permease by EIIA Glc ceases, and 3) the concentration of cAMP rises because the increase in the concentration of the phosphorylated form of EIIA Glc activates adenyl cyclcase This system displays positive feedback ( Aggarwal and Narang, 2022 ). As soon as amounts of permease and beta galactosidase get high enough, the cells will be able to sustain themselves by metabolizing lactose, and growth will resume.…”

Section: Introductionmentioning

confidence: 99%

The impact of metabolism on the adaptation of organisms to environmental change

Rothman

Moore

Shulman

2023

Front. Cell Dev. Biol.

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Since Jacob and Monod’s discovery of the lac operon ∼1960, the explanations offered for most metabolic adaptations have been genetic. The focus has been on the adaptive changes in gene expression that occur, which are often referred to as “metabolic reprogramming.” The contributions metabolism makes to adaptation have been largely ignored. Here we point out that metabolic adaptations, including the associated changes in gene expression, are highly dependent on the metabolic state of an organism prior to the environmental change to which it is adapting, and on the plasticity of that state. In support of this hypothesis, we examine the paradigmatic example of a genetically driven adaptation, the adaptation of E. coli to growth on lactose, and the paradigmatic example of a metabolic driven adaptation, the Crabtree effect in yeast. Using a framework based on metabolic control analysis, we have reevaluated what is known about both adaptations, and conclude that knowledge of the metabolic properties of these organisms prior to environmental change is critical for understanding not only how they survive long enough to adapt, but also how the ensuing changes in gene expression occur, and their phenotypes post-adaptation. It would be useful if future explanations for metabolic adaptations acknowledged the contributions made to them by metabolism, and described the complex interplay between metabolic systems and genetic systems that make these adaptations possible.

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Section: Introductionmentioning

confidence: 99%

The impact of metabolism on the adaptation of organisms to environmental change

Rothman

Moore

Shulman

2023

Front. Cell Dev. Biol.

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Inducer exclusion, by itself, cannot account for the glucose-mediated lac repression of Escherichia coli

Aggarwal

Narang

2022

Biophysical Journal

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Optimized Enzyme Production for the Escherichia coli Whole-Cell Biocatalytic Synthesis of Codeine from Thebaine

Jahanian,

Velasquez Agudelo,

Luna-Flores

et al. 2024

Org. Process Res. Dev.

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Codeine, the most widely used medicinal opiate in the world, can be produced from thebaine by using an environmentally friendly biocatalytic process using purified enzymes or microbial cells. However, this biotransformation is either inefficient or not systematically characterized for industrial use, as microbial fermentation and enzyme expression have not been optimized, and the production of the undesirable side product neopine reduces yields. In this study, the expression of the required enzymes in a reengineeredEscherichia coli system was optimized using a two-step design of experiments approach. Higher yields of biomass and enzyme expression were achieved in a defined minimal medium using lactose for induction. The interaction between temperature and lactose concentration was optimized, leading to an improvement in the apparent volumetric activity of thebaine 6-O-demethylase (T6ODM) from 45 to 776 U·L–1 using glycerol as the carbon source and an improvement in the apparent volumetric activity of codeinone reductase (COR) from 120 to 3707 U·L–1 using glucose. The productivity for T6ODM and COR was also increased 4.5 and 5.7-times to 8.0 and 28.3 U·L–1·h–1, respectively, in fed-batch cultivations compared to in shake flasks. With the optimized conditions for enzyme expression, the whole-cell biotransformation led to an 80% yield of codeine from thebaine and a final codeine/neopine molar ratio of 85:15. The inclusion of coexpressed neopinone isomerase, which catalyzes the production of codeinone from neopinone, reduced neopine production at the start of the reaction when the concentration of neopinone was low but did not improve the final codeine/neopine ratio as the reaction progressed and the concentration of neopinone increased. This observation may provide a further understanding of the differences between catalytic conditions in a bioreactor and the poppy plant, where the concentration of pathway intermediates such as neopinone is likely to be low and no neopine is observed. Overall, the process improvements reported here provide progress toward an industrial biocatalytic production of codeine from thebaine.

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Positive feedback exists and drives the glucose-mediated repression in Escherichia coli

Cited by 3 publications

References 39 publications

The impact of metabolism on the adaptation of organisms to environmental change

The impact of metabolism on the adaptation of organisms to environmental change

Inducer exclusion, by itself, cannot account for the glucose-mediated lac repression of Escherichia coli

Optimized Enzyme Production for the Escherichia coli Whole-Cell Biocatalytic Synthesis of Codeine from Thebaine

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