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A cluster of up-regulated genes on chromosome 7. See Fig 1 for explanation of the colouring of the tracks. https://doi.org/10.1371/journal.pone.0190913.g006
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Eukaryotes, including the unicellular eukaryotes such as yeasts, employ multiple levels of gene regulation. Regulation of chromatin structure through chromatin compaction cascades, and influenced by transcriptional insulators, might play a role in the coordinated regulation of genes situated at adjacent loci and expressed as a co-regulated cluster....
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Understanding how the packaging of chromatin in the nucleus is regulated and organized to guide cellular programs, complex developmental programs and responses to environmental cues is a major question in biology. Technological advances have allowed a remarkable progress within this field over the last years. However, we still know very little how...
Citations
... Multiplexed CRISPR interference (CRISPRi) and genes knockdown: for redirecting carbon flux of central metabolic pathways toward ethyl acetate production [157] Genome editing in Kluyveromyces and Ogataea yeasts using a broad-host-range Cas9/gRNA co-expression plasmid Development of a new CRISPR / Cas9 system based on plasmid-borne expression of Cas9 and a ribozymeflanked guide RNA molecule (gRNA) [158] Genetic and physiological basis for antibody production Disruption of the INU1 gene CRISPR-Cas9 for singlechain antibody (scFv) production and genomic integration [159] Differential RNA-seq, multi-network analysis and metabolic regulation analysis Development of a Reactomica software for combining omic data with modeling and simulation [160] Gene regulation in the context of chromosomes Computational analysis of genomic and RNA-seq data to discover the presence of clusters of co-localized genes that are also co-regulated [161] Development of a broad-range promoter set for metabolic engineering in the thermotolerant K. marxianus ...
ABSTRACT
Kluyveromyces marxianus is an ascomycetous yeast which has shown promising results in cellu- losic ethanol and renewable chemicals production. It can survive on a variety of carbon sources under industrially favorable conditions due to its fast growth rate, thermotolerance, and acid tol- erance. K. marxianus, is generally regarded as a safe (GRAS) microorganism, is widely recognized as a powerhouse for the production of heterologous proteins and is accepted by the US Food and Drug Administration (USFDA) for its pharmaceutical and food applications. Since lignocellulo- sic hydrolysates are comprised of diverse monomeric sugars, oligosaccharides and potential metabolism inhibiting compounds, this microorganism can play a pivotal role as it can grow on lignocellulosic hydrolysates coping with vegetal cell wall derived inhibitors. Furthermore, advancements in synthetic biology, for example CRISPR-Cas9 (clustered regularly interspaced short palindromic repeats with Cas9)-mediated genome editing, will enable development of an engineered yeast for the production of biochemicals and biopharmaceuticals having a myriad of industrial applications. Genetic engineering companies such as Cargill, Ginkgo Bioworks, DuPont, Global Yeast, Genomatica, and several others are actively working to develop designer yeasts. Given the important traits and properties of K. marxianus, these companies may find it to be a suitable biocatalyst for renewable chemicals and fuel production on the large scale. This paper reviews the recent progress made with K. marxianus biotechnology for sustainable production of ethanol, and other products utilizing lignocellulosic sugars.
... RNA-seq data also suggest clusters of co-localized DEGs in K. marxianus. Regions of possible subtelomeric silencing are evident but are non-responsive to the carbon sources of glucose or xylose (Schabort et al. 2018). Additionally, glucose-or xylose-responsive clusters that are present far from telomeres contain some of the genes with the most significantly differential expression that encode enzymes involved in the utilization of alternative carbon sources such as inulinase. ...
Among the so-called non-conventional yeasts, Kluyveromyces marxianus has extremely potent traits that are suitable for industrial applications. Indeed, it has been used for the production of various enzymes, chemicals, and macromolecules in addition to utilization of cell biomass as nutritional materials, feed and probiotics. The yeast is expected to be an efficient ethanol producer with advantages over Saccharomyces cerevisiae in terms of high growth rate, thermotolerance and a wide sugar assimilation spectrum. Results of comprehensive analyses of its genome and transcriptome may accelerate studies for applications of the yeast and may further increase its potential by combination with recent biotechnological tools including the CRISPR/Cas9 system. We thus review published studies by merging with information obtained from comprehensive data including genomic and transcriptomic data, which would be useful for future applications of K. marxianus.
... Glucose repression on inulinase production by Kluyveromyces species has been reported, which involves transcription factors, where Mig1 serves as repressor and Adr1 as activator. The mechanism of repression of Mig1 is to recruit chromatin silencing proteins, such as Tup1, which leads to the silencing of chromatin [29], that is our best approximation to extrapolate the mechanism of repression on fructanase production by K. marxianus CF15 [29]. Therefore, the analysis of the model parameters allows to associate inhibition and catabolite repression phenomena to particular substrates and products concentrations. ...
... Glucose repression on inulinase production by Kluyveromyces species has been reported, which involves transcription factors, where Mig1 serves as repressor and Adr1 as activator. The mechanism of repression of Mig1 is to recruit chromatin silencing proteins, such as Tup1, which leads to the silencing of chromatin [29], that is our best approximation to extrapolate the mechanism of repression on fructanase production by K. marxianus CF15 [29]. Therefore, the analysis of the model parameters allows to associate inhibition and catabolite repression phenomena to particular substrates and products concentrations. ...
This study focuses on fructanase production in a batch reactor by a new strain isolated from agave juice (K. marxianus var. drosophilarum) employing different Agave tequilana fructan (ATF) concentrations as substrate. The experimental data suggest that the fructanase production may be inhibited or repressed by high substrate (50 g/L) and ethanol (20.7 g/L) concentrations present in culture medium. To further analyze these phenomena an unstructured kinetic mathematical model taking into account substrate and products inhibition was proposed and fitted. The mathematical model considers six reaction kinetics and the ethanol evaporation, and predicts satisfactorily the biomass, fructan, glucose, fructose, ethanol, and fructanase behavior for different raw material initial concentrations. The proposed model is the first to satisfactorily describe the production of fructanase from branched ATF with a new strain of K. marxianus.
... Since Mig1 is known to be a regulator of glucose repression in K. marxianus 8,51 as well as in S. cerevisiae 52,53 , the effects of MIG1-disrupted mutation on central carbon metabolism were focused on. The mutation caused changes in the transcriptional levels of most of the genes involved in central carbon metabolism (Fig. 4 and Supplementary Information File S1). ...
Kmmig1 as a disrupted mutant of MIG1 encoding a regulator for glucose repression in Kluyveromyces marxianus exhibits a histidine-auxotrophic phenotype. Genome-wide expression analysis revealed that only HIS4 in seven HIS genes for histidine biosynthesis was down-regulated in Kmmig1. Consistently, introduction of HIS4 into Kmmig1 suppressed the requirement of histidine. Considering the fact that His4 catalyzes four of ten steps in histidine biosynthesis, K. marxianus has evolved a novel and effective regulation mechanism via Mig1 for the control of histidine biosynthesis. Moreover, RNA-Seq analysis revealed that there were more than 1,000 differentially expressed genes in Kmmig1, suggesting that Mig1 is directly or indirectly involved in the regulation of their expression as a global regulator.
The yeast Kluyveromyces marxianus SLP1 has the potential for application in biotechnological processes because it can metabolize several sugars and produce high-value metabolites. K. marxianus SLP1 is a thermotolerant yeast isolated from the mezcal process, and it is tolerant to several cell growth inhibitors such as saponins, furan aldehydes, weak acids, and phenolics compounds. The genomic differences between dairy and non-dairy strains related to K. marxianus variability are a focus of research attention, particularly the pathways leading this species toward polyploidy. We report the diploid genome assembly of K. marxianus SLP1 non-lactide strain into 32 contigs to reach a size of ∼12 Mb (N50 = 1.3Mb) and a ∼39% GC content. Genome size is consistent with the k-mer frequency results. Genome annotation by Funannotate estimated 5000 genes in haplotype A and 4910 in haplotype B. The enriched annotated genes by ontology show differences between alleles in biological processes and cellular component. The analysis of variants related to DMKU3 and between haplotypes shows changes in LAC12 and INU1, which we hypothesize can impact carbon source performance. This report presents the first polyploid K. marxianus strain recovered from non-lactic fermenting medium.
