Biology subjects

Uttenweiler-Joseph, S.

Publications and source records attributed to Uttenweiler-Joseph, S..

3 recordsLinked to original sources

bioRxiv2025

Acetate as a metabolic booster for glucose-based bioproduction in Escherichia coli

Escherichia coli, a key workhorse in industrial biotechnology, is commonly grown on glucose, which supports rapid growth but leads to acetate overflow, which instead inhibits growth, diverts carbon from the production pathway, and reduces productivity. Recent studies suggest that acetate may also have beneficial effects in glucose-grown E. coli, but its potential in bioprocesses remains unexplored. In this study, we systematically investigated acetates impact on bioproduction using a kinetic model of glucose and acetate metabolism in E. coli. The model predicts that acetate can enhance bioproduction in glucose-grown E. coli through three mechanisms: (i) by minimizing acetate overflow, thereby reducing carbon loss, (ii) by increasing acetyl-CoA levels, thereby boosting the biosynthetic flux of acetyl-CoA-derived compounds, and (iii) by promoting biomass accumulation, thus improving overall productivity. We experimentally validated the predictions of the model for mevalonate and 3-hydroxypropionate production, where acetate supplementation increased productivity by 117% and 34%, respectively. Our findings provide a valuable framework for optimizing E. coli-based bioprocesses and highlight acetates underutilized potential in biotechnology. By leveraging acetate from waste streams as a metabolic booster, this approach could contribute to more sustainable and environmentally friendly bioprocesses. Highlights- A kinetic model was used for rational optimization of E. coli-based bioprocesses - Acetate can enhance growth and production of acetyl-CoA-derived bioproducts - Model predictions were validated for mevalonate and 3-hydroxypropionate production - Acetate can be used as a metabolic booster for glucose-based bioproduction in E. coli

systems biology↗

bioRxiv2022

From toxic waste to beneficial nutrient: acetate boosts Escherichia coli growth at low glycolytic flux

Acetate, a major by-product of glycolytic metabolism in Escherichia coli and many other microorganisms, has long been considered a toxic waste compound that inhibits microbial growth. This counterproductive auto-inhibition represents a major problem in biotechnology and has puzzled the scientific community for decades. Recent studies have revealed that acetate is also a co-substrate of glycolytic nutrients and a global regulator of E. coli metabolism and physiology. Here, we used a systems biology strategy to investigate the mutual regulation of glycolytic and acetate metabolism. Computational and experimental results demonstrate that reducing the glycolytic flux enhances co-utilization of acetate with glucose. Acetate metabolism thus compensates for the reduction in glycolytic flux and eventually buffers carbon uptake so that acetate, far from being toxic, actually enhances E. coli growth under these conditions. We validated this mechanism using three orthogonal strategies: chemical inhibition of glucose uptake, glycolytic mutant strains, and alternative substrates with a natively low glycolytic flux. Acetate makes E. coli more robust to glycolytic perturbations and is a valuable nutrient, with a beneficial effect on microbial growth.

systems biology↗

bioRxiv2020

Control and regulation of acetate overflow in Escherichia coli

Overflow metabolism refers to the production of seemingly wasteful by-products by cells during growth on glucose even when oxygen is abundant. Two theories have been proposed to explain acetate overflow in Escherichia coli - global control of the central metabolism and local control of the acetate pathway - but neither accounts for all observations. Here, we develop a kinetic model of E. coli metabolism that quantitatively accounts for observed behaviors and successfully predicts the response of E. coli to new perturbations. We reconcile these theories and clarify the origin, control and regulation of the acetate flux. We also find that, in turns, acetate regulates glucose metabolism by coordinating the expression of glycolytic and TCA genes. Acetate should not be considered a wasteful end-product since it is also a co-substrate and a global regulator of glucose metabolism in E. coli. This has broad implications for our understanding of overflow metabolism.

systems biology↗