Improved Succinate Production by Metabolic Engineering

Abstract

Succinate is a promising chemical which has wide applications and can be produced by biological route. The history of the biosuccinate production shows that the joint effort of different metabolic engineering approaches brings successful results. In order to enhance the succinate production, multiple metabolical strategies have been sought. In this review, different overproducers for succinate production, including natural succinate overproducers and metabolic engineered overproducers, are examined and the metabolic engineering strategies and performances are discussed. Modification of the mechanism of substrate transportation, knocking-out genes responsible for by-products accumulation, overexpression of the genes directly involved in the pathway, and improvement of internal NADH and ATP formation are some of the strategies applied. Combination of the appropriate genes from homologous and heterologous hosts, extension of substrate, integrated production of succinate, and other high-value-added products are expected to bring a desired objective of producing succinate from renewable resources economically and efficiently.

Anodic respiration of Pseudomonas putida KT2440 in a stirred-tank bioreactor

“…Anaerobic processes can be operated with lower energy input but show formation of unwanted by-products [2]. Microorganisms form by-products to balance their redox metabolism [3] which reduces yields and can cause product inhibition [4][5][6]. An alternative may be offered by electro-fermentation, where an electrode provides an electron source or sink to overcome bottlenecks or drive fermentations towards particular desired products [7,8].…”

Interconnection between tricarboxylic acid cycle and energy generation in microbial fuel cell performed by desulfuromonas acetoxidans IMV B-7384

“…The citric acid cycle (TCA) or Krebs cycle, is a process utilized by numerous organisms to generate energy via the oxidation of acetate derived from carbohydrates, fats, and proteins into carbon dioxide 13 . The TCA cycle operates during aerobic and anaerobic respiration or fermentation by running in an oxidative cycle (when respiring oxygen) or in an incomplete, reductive, and branched pathway, respectively ( fig.1) 13 .…”

“…The TCA cycle operates during aerobic and anaerobic respiration or fermentation by running in an oxidative cycle (when respiring oxygen) or in an incomplete, reductive, and branched pathway, respectively ( fig.1) 13 . There are numerous anaerobic organisms that utilize a reverse TCA cycle.…”

“…It is assumed that Desulfuromonas acetoxidans bacterium is able to perform the reductive TCA under anaerobic conditions. At anoxic conditions, succinate serves the H-acceptor instead of oxygen, and therefore the reductive branch of the TCA cycle is used 13 The pathway converts oxaloacetate to malate, fumarate, and then succinate, which requires 2 moles of NADH per mole of succinate produced [14][15][16][17] . The equation of anaerobic pathway is (2) 13 :…”

“…1,4-butanediol-based polymers have better properties and greater stability in comparison to polymers produced from 1,2-propanediol or ethylene glycol. Further, CO 2 is assimilated during the succinate biosynthesis which can be considered as an environmental advantage 13 .…”