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Related Concept Videos

Products of the Citric Acid Cycle00:53

Products of the Citric Acid Cycle

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The cells of most organisms—including plants and animals—obtain usable energy through aerobic respiration, the oxygen-requiring version of cellular respiration. Aerobic respiration consists of four major stages: glycolysis, pyruvate oxidation, the citric acid cycle, and oxidative phosphorylation. The third major stage, the citric acid cycle, is also known as the Krebs cycle or tricarboxylic acid (TCA) cycle.
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The Citric Acid Cycle: Output01:28

The Citric Acid Cycle: Output

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The citric acid cycle is termed an amphibolic pathway as it operates both anabolically and catabolically. The cyclic reactions balance the flux of the substrates to provide an optimal concentration of NADH and ATP to the cell.
Regulation of Citric Acid Cycle
The citric acid cycle is regulated in several ways, including feedback inhibition, regulation of enzyme activities, and associated anaplerotic or cataplerotic pathways.
The primary substrate of the TCA cycle—acetyl CoA—is...
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The Citric Acid Cycle: Overview01:37

The Citric Acid Cycle: Overview

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In aerobic organisms, the citric acid cycle is the second stage of cellular respiration wherein molecules derived from the breakdown of carbohydrates, proteins, and fats are oxidized into carbon dioxide and energy. This process is also known as the tricarboxylic acid (TCA) cycle as the first product of the cycle, citric acid, contains three carboxyl groups in its structure. Alternatively, this cycle is also referred to as the Krebs cycle, in honor of its discoverer Sir Hans Krebs.
The citric...
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Fates of Pyruvate01:20

Fates of Pyruvate

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Pyruvate is the end product of glycolysis, where glucose is oxidized to pyruvate, simultaneously reducing NAD+ to NADH. Two molecules of ATP are also produced by substrate-level phosphorylation.
In aerobic organisms, pyruvate is metabolized via the citric acid cycle to produce reduced coenzymes NADH and FADH2. These coenzymes are then oxidized in the electron transport chain to produce ATP and, in the process, regenerate the NAD+ and FAD. As seen in some cell types and organisms, fermentation...
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Other Glycolytic Pathways01:24

Other Glycolytic Pathways

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The pentose phosphate pathway (PPP) operates in parallel with glycolysis, facilitating the metabolism of both pentoses and glucose. This pathway consists of two distinct phases: the oxidative and non-oxidative phases. While it does not directly generate ATP, the intermediates formed during the process can integrate into glycolysis, contributing to cellular energy metabolism when required.Oxidative Phase: NADPH ProductionThe oxidative phase of the pentose phosphate pathway is primarily...
103
The Citric Acid Cycle02:36

The Citric Acid Cycle

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The citric acid cycle, also known as the Krebs cycle or TCA cycle, consists of several energy-generating reactions that yield one ATP molecule, three NADH molecules, one FADH2 molecule, and two CO2 molecules.
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Related Experiment Video

Updated: Aug 14, 2025

A Toolkit to Enable Hydrocarbon Conversion in Aqueous Environments
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Caffeic acid production from glucose using metabolically engineered Escherichia coli.

Kosuke Sakae1, Daisuke Nonaka1, Mayumi Kishida1

  • 1Department of Chemical Science and Engineering, Graduate School of Engineering, Kobe University, 1-1 Rokkodai, Nada, Kobe 657-8501, Japan.

Enzyme and Microbial Technology
|January 9, 2023
PubMed
Summary

Engineered Escherichia coli efficiently produces caffeic acid directly from glucose. This microbial platform achieves high yields, offering a sustainable source for valuable compounds in pharmaceuticals and cosmetics.

Keywords:
Caffeic acidE. coliMetabolic engineeringShikimate pathwayp-coumaric acid

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Area of Science:

  • Biotechnology
  • Metabolic Engineering
  • Microbial Production

Background:

  • Caffeic acid is a valuable precursor for pharmaceuticals, cosmetics, and food additives due to its anticancer, antiviral, and anti-inflammatory properties.
  • Current production methods are often inefficient or rely on costly precursors.
  • Developing a microbial fermentation process for direct caffeic acid production from simple sugars is highly desirable.

Purpose of the Study:

  • To engineer an Escherichia coli strain for the direct and high-level production of caffeic acid from glucose.
  • To optimize the metabolic pathway for enhanced caffeic acid biosynthesis.
  • To establish a robust fermentation process for scalable caffeic acid production.

Main Methods:

  • Expression of key enzymes: Tyrosine ammonia-lyase (RgTAL) and p-coumaric acid 3-hydroxylase (SeC3H).
  • Introduction of feedback-resistant chorismate mutase/prephenate dehydrogenase to boost L-tyrosine synthesis.
  • Metabolic engineering to reduce intermediate accumulation by introducing 4-hydroxyphenylacetate 3-hydroxylase (PaHpaBC).

Main Results:

  • An engineered strain (CA3) produced 1.58 g/L of caffeic acid from glucose without supplementation.
  • A further engineered strain (CA8) achieved a final yield of 6.17 g/L of caffeic acid from glucose in a jar fermenter.
  • The developed E. coli strain serves as an effective chassis for producing caffeic acid and its derivatives.

Conclusions:

  • Metabolic engineering of E. coli enables efficient direct production of caffeic acid from glucose.
  • The engineered strain demonstrates significant potential for industrial-scale biosynthesis of caffeic acid.
  • This microbial platform offers a sustainable and cost-effective route for producing valuable caffeic acid-based compounds.