Study of the growth of Escherichia coli on mixed substrates using dynamic flux balance analysis

Abstract

Escherichia coli produces acetate as the major by-product when grown in a batch culture medium of glucose under aerobic conditions. The secreted acetate can be used as an additional substrate for cell growth leading to a mixed-substrate growth pattern of diauxic growth. However the acetate formed can limit growth of the organism if found in high amounts in the culture medium and such a scenario necessitates the study of the growth of microorganisms on mixed substrates. Dynamic flux balance analysis has turned out to be a promising tool in capturing such scenarios of growth on mixed substrates. In this study we carry out a dynamic flux balance analysis study of the growth of Escherichia coli in a batch culture medium of glucose and acetate where the organism encounters the presence of mixed substrates. Additionally we have used a detailed metabolic network to describe the process of metabolism in the organism Escherichia coli. DFBA combined with such detailed metabolic networks can open up possibilities of preventing such harmful growth scenarios for biotechnologically useful micro-organisms.

Dynamic flux balance analysis of high cell density fed‐batch culture of Escherichia coli BL21 (DE3) with mass spectrometry‐based spent media analysis

“…Dynamic flux balance analysis (dynamic FBA), involving dynamic and static optimization approaches, was developed to analyze the diauxic profile of E. coli on glucose and acetate (Mahadevan et al, 2002) by analyzing fluxes over time. Dynamic FBA has been since used in several studies to simulate E. coli cellular metabolism in multisubstrate environments using defined (Feng et al, 2012; Joy & Kremling, 2010) and complex media (Meadows et al, 2010; Zampieri et al, 2019). However, these studies were either limited to batch fermentations or used a much simplified metabolic model, which does not reflect a true industrial process.…”

“…Dynamic FBA has been since used in several studies to simulate E. coli cellular metabolism in multisubstrate environments using defined (Feng et al, 2012;Joy & Kremling, 2010) and complex media (Meadows et al, 2010;Zampieri et al, 2019). However, these studies were either limited to batch fermentations or used a much simplified metabolic model, which does not reflect a true industrial process.…”