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Alleviating glucose repression and enhancing respiratory capacity to increase itaconic acid production

Synthetic and Systems Biotechnology 2023年第1期8卷 129-140页

作者： Yaying Xu Zhimin Li State Key Laboratory of Bioreactor Engineering East China University of Science and Technology130 Meilong RoadShanghai200237China Shanghai Collaborative Innovation Center for Biomanufacturing Technology 130 Meilong RoadShanghai200237China

The Crabtree effect products ethanol and acetic acid can be used for itaconic acid(IA)production in Saccharomyces ***,both the IA synthesis and oxidative phosphorylation pathways were hampered by glucose repression when glucose was used as the *** study aimed to improve IA titer by increasing gene expressions related to glucose derepression without impairing yeast growth on *** the acetyl-CoA synthesis pathway increased the titer of IA to 257 mg/L in a urea-based *** of entire pathway overexpression,we found that some signaling pathways regulating glucose repression were effective targets to improve IA production and respiratory *** a consequence of the reduced inhibition,IA titer was further increased by knocking out a negative regulator of the mitochondrial retrograde signaling ***1/MIG1 signaling was disturbed by deleting the hexokinase HXK2 or an endoplasmic reticulum membrane protein *** shaking results showed that XYY286(BY4741,HO::cadA,Y::***,208a::***,Δhxk2,pRS415-cadA,pRS423-aac2)accumulated 535 mg/L IA in 168 h in the YSCGLU ***-PCR results verified that deletion of MKS1 or HXK2 upregulated the gene expressions of the IA synthesis and respiratory pathways during the growth on glucose.

关键词： Itaconic acid glucose repression Signaling pathway

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Inositol and Phosphatidylinositol Mediated glucose Derepression, Gene Expression and Invertase Secretion in Yeasts

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Acta Biochimica et Biophysica Sinica 2004年第7期36卷 443-449页

作者： Zhen-Ming CHI*, Jun-Feng LI, Xiang-Hong WANG, and Shu-Min YAOUNESCO Chinese Center of Marine Biotechnology, Ocean University of China, Qingdao 266003, China UNESCO Chinese Center of Marine Biotechnology Ocean University of ChinaQingdao 266003 China

glucose repression occurs in many yeast species and some filamentous fungi, and it represses the expression and secretion of many intracellular and extracellular proteins. In recent years, it has been found that many biochemical reactions in yeast cells are mediated by phosphatidylinositol (PI)-type signaling pathway. However, little is known about the relationships between PI-type signaling and glucose repression, gene expression and invertase secretion in yeasts. Many evidences in our previous studies showed that glucose repression, invertase secretion, gene expression and cell growth were mediated by inositol and PI in Saccharomyces and Schizosaccharomyces. The elucidation of the new regulatory mechanisms of protein secretion, gene expression and glucose repression would be an entirely new aspect of inositol and PI-type signaling regulation in yeasts.

关键词： glucose repression PI-type signaling pathway invertase secretion gene expression

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Profiling proteomic responses to hexokinase-II depletion in terpene-producing Saccharomyces cerevisiae

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Engineering Microbiology 2023年第3期3卷 1-13页

作者： Zeyu Lu Qianyi Shen Lian Liu Gert Talbo Robert Speight Matt Trau Geoff Dumsday Christopher B.Howard Claudia E.Vickers Bingyin Peng ARC Centre of Excellence in Synthetic Biology Queensland University of TechnologyBrisbaneQLD4000Australia Australian Institute for Bioengineering and Nanotechnology(AIBN) The University of QueenslandBrisbaneQLD4072Australia Centre of Agriculture and the Bioeconomy School of Biology and Environmental ScienceFaculty of ScienceQueensland University of TechnologyBrisbaneQLD4000Australia CSIRO Synthetic Biology Future Science Platform Commonwealth Scientific and Industrial Research Organisation(CSIRO)Black MountainACT2601Australia School of Chemistry and Molecular Biosciences(SCMB) the University of QueenslandBrisbaneQLD4072Australia Metabolomics Australia(Queensland Node) Australian Institute for Bioengineering and Nanotechnology(AIBN)The University of QueenslandBrisbaneQLD4072Australia CSIRO Manufacturing ClaytonVIC3169Australia Eden Brew Pty Ltd GlenorieNSW2157Australia

Hexokinase II(Hxk2)is a master protein in glucose-mediated transcriptional repression signaling ***-grading Hxk2 through an auxin-inducible protein degradation previously doubled sesquiterpene(nerolidol)pro-duction at gram-per-liter levels in Saccharomyces *** transcriptomics/proteomics profiles in Hxk2-deficient background are important to understanding genetic and molecular mechanisms for improved nerolidol production and guiding further strain ***,proteomic responses to Hxk2 depletion are investi-gated in the yeast strains harboring a GAL promoters-controlled nerolidol synthetic pathway,at the exponential and ethanol growth phases and in GAL80-wildtype and gal80Δ*** metabolic pathways and amino acid metabolic pathways show diversified responses to Hxk2 depletion and growth on ethanol,including upregulation of alternative carbon catabolism and respiration as well as downregulation of amino acid ***-repression of GAL genes may contribute to improved nerolidol production in Hxk2-depleted ***-teen transcription factors associated with upregulated genes are *** Ash1-mediated repression on the RIM4 promoter shows the variation on the regulatory effects of different Ash1-binding sites and the syner-gistic effect of Ash1 and Hxk2-mediated *** validation of individual promoters shows that HXT1 promoter activities are glucose-dependent in hxk2Δbackground,but much weaker than those in HXK2-wildtype *** summary,inactivating HXK2 may relieve glucose repression on respiration and GAL promoters for improved bioproduction under aerobic conditions in *** proteomics profiles provide a better genetics overview for a better metabolic engineering design in Hxk2-deficient backgrounds.

关键词： Proteomics glucose repression Metabolic engineering Crabtree effect Sesquiterpene Synthetic biology Genetic regulation

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