Engineering the glyoxylate cycle for chemical bioproduction

Abstract

With growing concerns about environmental issues and sustainable economy, bioproduction of chemicals utilizing microbial cell factories provides an eco-friendly alternative to current petro-based processes. Creating high-performance strains (with high titer, yield, and productivity) through metabolic engineering strategies is critical for cost-competitive production. Commonly, it is inevitable to fine-tuning or rewire the endogenous or heterologous pathways in such processes. As an important pathway involved in the synthesis of many kinds of chemicals, the potential of the glyoxylate cycle in metabolic engineering has been studied extensively these years. Here, we review the metabolic regulation of the glyoxylate cycle and summarize recent achievements in microbial production of chemicals through tuning of the glyoxylate cycle, with a focus on studies implemented in model microorganisms. Also, future prospects for bioproduction of glyoxylate cycle-related chemicals are discussed.

Artificial switches induce the bespoke production of functional compounds in marine microalgae Chlorella by neutralizing CO2

“…Meanwhile, transcripts of genes relating to glyoxylate cycle, such as isocitrate lyase ( aceA , CP3g3555) and malate synthase (MLS, CP3g2923), were increased in the mutant (Fig. 6 ; Additional file 2 : Table S3), which potentially contribute to biomass generation by conserving carbon skeletons via bypassing the oxidative decarboxylation steps of the citrate cycle [ 40 ]. Therefore, the choreography of the transcripts was concomitant with the increase in lipid synthesis and the decrease in the synthesis of starch and proteins in the mutant, suggesting that these genes are responsible for carbon shift from sugars and proteins to lipid synthesis.…”

Exploring salivary metabolome alterations in people with HIV: towards early diagnostic markers

“…The glyoxylate cycle in glyoxylate and dicarboxylate metabolism represents the conversion of fat to sugar, commonly considered as an ancillary route to the TCA cycle, which is central to cellular metabolism. Conversely, the TCA cycle occurs in mitochondria and is closely associated with oxidative decarboxylation of sugars ( 21 , 22 ). The TCA cycle, being central to carbon and energy metabolism and a primary source of cellular energy, has been found to have its intermediates in serum acting as biomarkers for various potential pathological conditions ( 23 , 24 ).…”

Efficient Plant Triterpenoids Synthesis in Saccharomyces cerevisiae: from Mechanisms to Engineering Strategies

“…The glyoxylate cycle plays an important role in cell growth and metabolism, and the primary function is to enable cells to utilize ethanol and acetate in the absence of glucose. 59 First, the cells can utilize carbon source of C 2 compounds (e.g., ethanol and acetate), and the physiological action of the glyoxylate cycle is to convert acetyl-CoA into C4 metabolites intermediate, which can continue to perform cellular reactions including amino acid biosynthesis and gluconeogenesis. 60 In S. cerevisiae, the glyoxylate cycle involves multiple steps of complex enzymatic reactions that occur primarily in the cytoplasm and peroxisomes.…”

“…The glyoxylate cycle, an anaplerotic variant of the tricarboxylic acid (TCA) cycle, is an important anabolic pathway in S. cerevisiae . The glyoxylate cycle plays an important role in cell growth and metabolism, and the primary function is to enable cells to utilize ethanol and acetate in the absence of glucose . First, the cells can utilize carbon source of C 2 compounds (e.g., ethanol and acetate), and the physiological action of the glyoxylate cycle is to convert acetyl-CoA into C4 metabolites intermediate, which can continue to perform cellular reactions including amino acid biosynthesis and gluconeogenesis .…”