scholarly journals Directed yeast genome evolution by controlled introduction of trans-chromosomic structural variations

2021 ◽  
Author(s):  
Bin Jia ◽  
Jin Jin ◽  
Mingzhe Han ◽  
Ying-Jin Yuan
Keyword(s):  
Genome Evolution ◽  
Rational Design ◽  
Chromosome Rearrangement ◽  
Genomic Variation ◽  
Yeast Genome ◽  
Structural Variations ◽  
Heterologous Biosynthesis ◽  
Naturally Occurring ◽  
3D Architecture ◽  
Random Screen

Background: Naturally occurring structural variations (SVs) are a considerable source of genomic variation and can reshape chromosomes 3D architecture. The synthetic chromosome rearrangement and modification by loxP-mediated evolution (SCRaMbLE) system has been proved to generate random SVs to impact phenotypes and thus constitutes powerful drivers of directed genome evolution. However, controllable methods to introduce complex SVs and revealing the related molecular mechanism has so far remained challenging. Results: We develop a SV-prone yeast strain by using SCRaMbLE with two synthetic chromosomes, synV and synX. An heterologous biosynthesis pathway allowing a high throughput screen for increased yield of astaxanthin is used as readout and a proof of concept for the application of SV in industry. We report here that complex SVs, including a pericentric inversion and a trans-chromosomes translocation between synV and synX, result in two neochromosomes and a 2.7-fold yield of astaxanthin. We mapped genetic targets contributing to higher astaxanthin yield and demonstrated the SVs can led to large reorganization of the genetic information along the chromosomes. We also used the model learned from the aforementioned random screen and successfully harnessed the precise introduction of trans-chromosomes translocation and pericentric inversions by rational design. Conclusions: Our work provides an effective tool to not only accelerate the directed genome evolution but also reveal mechanistic insight of complex SVs for altering phenotypes.

scholarly journals Genomic Variation between PRSV Resistant Transgenic SunUp and Its Progenitor Cultivar Sunset

2020 ◽  
Author(s):  
Jingping Fang ◽  
Andrew Wood ◽  
Youqiang Chen ◽  
Jingjing Yue ◽  
Ray Ming
Keyword(s):  
Spontaneous Mutation ◽  
Nuclear Genome ◽  
Plastid Dna ◽  
High Impact ◽  
Genomic Variation ◽  
Reliable Estimate ◽  
Nucleotide Polymorphisms ◽  
Structural Variations ◽  
Transgenic Papaya ◽  
Organelle Genomes

Abstract Background: The safety of genetically transformed plants remains a subject of scrutiny. Genomic variants in PRSV resistant transgenic papaya will provide evidence to rationally address such concerns. Results: In this study, a total of more than 74 million Illumina reads for progenitor ‘Sunset’ were mapped onto transgenic papaya ‘SunUp’ reference genome. 310,364 single nucleotide polymorphisms (SNPs), 34,071 small Inserts/deletions (InDels) and 1,200 large structural variations (SVs) were detected between ‘Sunset’ and ‘SunUp’. Those variations have an uneven distribution across nine chromosomes in papaya. Only 0.27% of mutations were predicted to be high-impact mutations. ATP-related categories were highly enriched among these high-impact genes. The SNP mutation rate was about 8.4×10-4 per site, comparable with the rate induced by spontaneous mutation over numerous generations. The transition-to-transversion ratio was 1.439 and the predominant mutations were C/G to T/A transitions. Spontaneous mutations were the leading cause of SNPs in transgenic papaya ‘SunUp’. A total of 3,430 nuclear plastid DNA (NUPT) and 2,764 nuclear mitochondrial DNA (NUMT) junction sites have been found in ‘SunUp’, which is proportionally higher than the predicted total NUPT and NUMT junction sites in ‘Sunset’ (3,346 and 2,745, respectively). Among all nuclear organelle DNA (norgDNA) junction sites, 96% of junction sites were shared by ‘SunUp’ and ‘Sunset’. The average identity between ‘SunUp’ specific norgDNA and corresponding organelle genomes was higher than that of norgDNA shared by ‘SunUp’ and ‘Sunset’. Six ‘SunUp’ organelle-like borders of transgenic insertions were nearly identical to corresponding sequences in organelle genomes (98.18~100%). None of the paired-end spans of mapped ‘Sunset’ reads were elongated by any ‘SunUp’ transformation plasmid derived inserts. Significant amounts of DNA were transferred from organelles to the nuclear genome during bombardment, including the six flanking sequences of the three transgenic insertions.Conclusions: Comparative whole-genome analyses between ‘SunUp’ and ‘Sunset’ provide a reliable estimate of genome-wide variations and evidence of organelle-to-nucleus transfer of DNA associated with biolistic transformation.

scholarly journals Rational Design for Mn3O4@carbon Foam Nanocomposite with 0D@3D Structure for Boosting Electrochemical Performance

2020 ◽  
Author(s):  
Zhu Yihan ◽  
Dongfeng Wang ◽  
Xuehua Yan ◽  
Yanli Li ◽  
Wending Zhou ◽  
...  
Keyword(s):  
Electrochemical Performance ◽  
Current Density ◽  
Rational Design ◽  
Hydrothermal Reaction ◽  
3D Structure ◽  
Carbon Foam ◽  
Transfer Path ◽  
3D Architecture ◽  
One Step ◽  
Mn3o4 Nanoparticles

Abstract A rational strategy was developed to prepare a nanocomposite with 0D/3D architecture. The composite containing Mn3O4 nanoparticles (0D) and carbon foam (3D) could be applied as an electrode material for supercapacitor by taking advantage of high conductivity of carbon foam (CF) and high pseudocapacitance of Mn3O4 nanoparticles. CF was prepared by a carbonization method using melamine foam, and then Mn3O4 nanoparticles were combined with carbon foam by a one-step hydrothermal method to prepare Mn3O4@CF nanocomposite. The 0D@3D hierarchical structure of Mn3O4@CF nanocomposite using CF as a 3D growing skeleton prevents agglomeration and increases reactive sites of Mn3O4 nanoparticles. In addition, CF as a conductive skeleton shortens the charge transfer path. The synergistic effect between CF and Mn3O4 improves the electrochemical performance of CF. Three Mn3O4@CF composites were prepared by adjusting the mass of the reactants in the processes of hydrothermal reaction. The Mn3O4 nanoparticles are uniformly grown on the CF surface with a diameter of 18 nm. Mn3O4@CF-2 composite has a specific capacitance of 212.8 F/g at a current density of 1 A/g, which is much higher than that of pristine CF (79.1 F/g) and Mn3O4 (112.7 F/g). The cyclic stability of Mn3O4@CF-2 is retained as 86.1% of initial capacitance after 2000 cycles at the current density of 1 A/g. It proves the feasibility of the as-mentioned strategy and broadens the application of carbon foam in supercapacitor.

Genomic Variation between PRSV Resistant Transgenic SunUp and Its Progenitor Cultivar Sunset Induced by Particle Bombardment Transformation

2019 ◽  
Author(s):  
Jingping Fang ◽  
Andrew Wood ◽  
Youqiang Chen ◽  
Jingjing Yue ◽  
Ray Ming
Keyword(s):  
Spontaneous Mutation ◽  
Nuclear Genome ◽  
Plastid Dna ◽  
High Impact ◽  
Genomic Variation ◽  
Reliable Estimate ◽  
Nucleotide Polymorphisms ◽  
Structural Variations ◽  
Transgenic Papaya ◽  
Organelle Genomes

Abstract The safety of genetically transformed plants remains a subject of scrutiny. Genomic variants in PRSV resistant transgenic papaya will provide evidence to rationally address such concerns. In this study, a total of more than 74 million Illumina reads for progenitor ‘Sunset’ were mapped onto transgenic papaya ‘SunUp’ reference genome. 310,364 single nucleotide polymorphisms (SNPs), 34,071 Small Inserts/deletions (InDels) and 1,200 large structural variations (SVs) were detected between ‘Sunset’ and ‘SunUp’. Those variations have an uneven distribution across nine chromosomes in papaya. Only 0.27% of mutations were predicted to be high-impact mutations. ATP-related categories were highly enriched among these high-impact genes. The SNP mutation rate was about 8.4×10 -4 per site, comparable with the rate induced by spontaneous mutation over numerous generations. The transition-to-transversion ratio was 1.439 and the predominant mutations were C/G to T/A transitions. Spontaneous mutations were the leading cause of SNPs in transgenic papaya ‘SunUp’. A total of 3,430 nuclear plastid DNA (NUPT) and 2,764 nuclear mitochondrial DNA (NUMT) junction sites have been found in ‘SunUp’, which is proportionally higher than the predicted total NUPT and NUMT junction sites in ‘Sunset’ (3,346 and 2,745, respectively). Among all nuclear organelle DNA (norgDNA) junction sites, 96% of junction sites were shared by ‘SunUp’ and ‘Sunset’. The average identity between ‘SunUp’ specific norgDNA and corresponding organelle genomes was higher than that of norgDNA shared by ‘SunUp’ and ‘Sunset’. Six ‘SunUp’ organelle-like borders of transgenic insertions were nearly identical to corresponding sequences in organelle genomes (98.18~100%). None of the paired-end spans of mapped ‘Sunset’ reads were elongated by any ‘SunUp’ transformation plasmid derived inserts. Significant amounts of DNA were transferred from organelles to the nuclear genome during bombardment, including the six flanking sequences of the three transgenic insertions. Comparative whole-genome analyses between ‘SunUp’ and ‘Sunset’ provide a reliable estimate of genome-wide variations and evidence of organelle-to-nucleus transfer of DNA associated with biolistic transformation.

scholarly journals Structural genome analysis in cultivated potato taxa

2019 ◽  
Vol 133 (3) ◽  
pp. 951-966 ◽  
Author(s):  
Maria Kyriakidou ◽  
Sai Reddy Achakkagari ◽  
José Héctor Gálvez López ◽  
Xinyi Zhu ◽  
Chen Yu Tang ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Copy Number ◽  
Agronomic Traits ◽  
Genomic Variation ◽  
Sequencing Data ◽  
Structural Variations ◽  
Structural Genomic ◽  
Ploidy Levels ◽  
Cultivated Potato ◽  
Number Variation

Abstract Key message Twelve potato accessions were selected to represent two principal views on potato taxonomy. The genomes were sequenced and analyzed for structural variation (copy number variation) against three published potato genomes. Abstract The common potato (Solanum tuberosum L.) is an important staple crop with a highly heterozygous and complex tetraploid genome. The other taxa of cultivated potato contain varying ploidy levels (2X–5X), and structural variations are common in the genomes of these species, likely contributing to the diversification or agronomic traits during domestication. Increased understanding of the genomes and genomic variation will aid in the exploration of novel agronomic traits. Thus, sequencing data from twelve potato landraces, representing the four ploidy levels, were used to identify structural genomic variation compared to the two currently available reference genomes, a double monoploid potato genome and a diploid inbred clone of S. chacoense. The results of a copy number variation analysis showed that in the majority of the genomes, while the number of deletions is greater than the number of duplications, the number of duplicated genes is greater than the number of deleted ones. Specific regions in the twelve potato genomes have a high density of CNV events. Further, the auxin-induced SAUR genes (involved in abiotic stress), disease resistance genes and the 2-oxoglutarate/Fe(II)-dependent oxygenase superfamily proteins, among others, had increased copy numbers in these sequenced genomes relative to the references.

scholarly journals Targeting of CXCR4 by the naturally occurring CXCR4 antagonist EPI-X 4 in Waldenström’s Macroglobulinemia

2020 ◽  
Author(s):  
Lisa M. Kaiser ◽  
Mirja Harms ◽  
Daniel Sauter ◽  
Vijay PS Rawat ◽  
Mirco Glitscher ◽  
...  
Keyword(s):  
Rational Design ◽  
Mapk Signaling ◽  
Migration And Invasion ◽  
Waldenström’S Macroglobulinemia ◽  
Cxcr4 Antagonist ◽  
Cxcr4 Signaling ◽  
Naturally Occurring ◽  
Waldenstrom's Macroglobulinemia ◽  
Waldenstrom’S Macroglobulinemia ◽  
Waldenström's Macroglobulinemia

AbstractCXCR4 expression and downstream signaling have been identified as key factors in malignant hematopoiesis. Thus, up to 40% of all patients with Waldenström’s Macroglobulinemia (WM) carry an activating mutation of CXCR4 that leads to a more aggressive clinical course and inferior outcome upon treatment with the Bruton’s tyrosine kinase inhibitor ibrutinib. Nevertheless, little is known about physiological mechanisms counteracting CXCR4 signaling in hematopoietic neoplasms. Recently, the endogenous human peptide EPI-X4 was identified as a natural CXCR4 antagonist that effectively blocks CXCL12-mediated receptor internalization and suppresses the migration and invasion of cancer cells towards a CXCL12 gradient. Here, we demonstrate that EPI-X4 efficiently impairs growth of WM cells in vitro and in vivo and blocks their migration towards CXCL12. The CXCR4 inhibitory activity of EPI-X4 is accompanied by decreased expression of genes involved in MAPK signaling and energy metabolism. Notably, the anti-WM activity of EPI-X4 could be further augmented by the rational design of EPI-X4 derivatives showing higher binding affinity to CXCR4. In summary, these data demonstrate that a naturally occurring anti-CXCR4 peptide is able to interfere with WM growth, and that optimized derivatives of EPI-X4 may represent a promising approach in suppressing growth promoting CXCR4 signaling in WM.

scholarly journals A Universal Chemical Method for Rational Design of Protein-based Nanoreactors

2021 ◽  
Author(s):  
Mullapudi Mohan Reddy ◽  
Punita Bathla ◽  
Britto S. Sandanaraj
Keyword(s):  
Self Assembly ◽  
Rational Design ◽  
Chemical Method ◽  
Living Cells ◽  
Protein Labeling ◽  
Self Assembling ◽  
Naturally Occurring ◽  
General Chemical ◽  
Chemical Strategy ◽  
Artificial Protein

AbstractSelf-assembly of a monomeric protease to form a multi-subunit protein complex “proteasome” enables targeted protein degradation in living cells. The naturally occurring proteasomes serve as an inspiration and blueprint for the design of artificial protein-based nanoreactors. Here we disclose a general chemical strategy for the design of proteasome-like nanoreactors. Micelle-assisted protein labeling (MAPLab) technology along with the N-terminal bioconjugation strategy is utilized for the synthesis of a well-defined monodisperse self-assembling semi-synthetic protease. The designer protein is programmed to self-assemble into a proteasome-like nanostructure which preserves the functional properties of native protease.

scholarly journals Yeast genome evolution—the origin of the species

Yeast ◽  
2007 ◽  
Vol 24 (11) ◽  
pp. 929-942 ◽  
Author(s):  
Devin R. Scannell ◽  
Geraldine Butler ◽  
Kenneth H. Wolfe
Keyword(s):  
Genome Evolution ◽  
Yeast Genome

scholarly journals Critical Synergistic Concentration of Lecithin Phospholipids Improves the Antimicrobial Activity of Eugenol against Escherichia coli

2017 ◽  
Vol 83 (21) ◽  
Author(s):  
Haoshu Zhang ◽  
Edward G. Dudley ◽  
Federico Harte
Keyword(s):  
Escherichia Coli ◽  
Foodborne Pathogens ◽  
Rational Design ◽  
Microbial Population ◽  
Critical Concentration ◽  
Antimicrobial Properties ◽  
Content Type ◽  
E Coli ◽  
Log Reduction ◽  
Naturally Occurring

ABSTRACT In this study, the effect of individual lecithin phospholipids on the antimicrobial properties of eugenol against Escherichia coli C600 was investigated. We tested five major phospholipids common in soy or egg lecithin (1,2-dihexadecanoyl-sn-glycero-3-phosphocholine [DPPC], 1,2-dioctadecanoyl-sn-glycero-3-phosphocholine [DSPC], 1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine [DPPE], 1,2-dihexadecanoyl-sn-glycero-3-phosphate [sodium salt] [DPPA], and 1,2-dihexadecanoyl-sn-glycero-3-phospho-l-serine [DPPS]) and one synthetic cationic phospholipid (1,2-dioctadecanoyl-sn-glycero-3-ethylphosphocholine [18:0 EPC]). Among the six phospholipids, DPPC, DSPC, DPPE, DPPA, and the cationic 18:0 EPC showed critical synergistic concentrations that significantly improved the inactivation effect of eugenol against E. coli after 30 min of exposure. At the critical synergistic concentration, an additional ca. 0.4 to 1.9 log reduction (ca. 0.66 to 2.17 log CFU/ml reduction) in the microbial population was observed compared to eugenol-only (control) treatments (ca. 0.25 log reduction). In all cases, increasing the phospholipid amount above the critical synergistic concentration (which was different for each phospholipid) resulted in antimicrobial properties similar to those seen with the eugenol-only (control) treatments. DPPS did not affect the antimicrobial properties of eugenol at the tested concentrations. The critical synergistic concentration of phospholipids was correlated with their critical micelle concentrations (CMC). IMPORTANCE Essential oils (EOs) are naturally occurring antimicrobials, with limited use in food due to their hydrophobicity and strong aroma. Lecithin is used as a natural emulsifier to stabilize EOs in aqueous systems. We previously demonstrated that, within a narrow critical-concentration window, lecithin can synergistically enhance the antimicrobial properties of eugenol. Since lecithin is a mixture of different phospholipids, we aimed to identify which phospholipids are crucial for the observed synergistic effect. This research studied the bioactivity of lecithin phospholipids, contributing to a rational design in using lecithin to effectively control foodborne pathogens in foods.

scholarly journals Development of highly efficient platinum catalysts for hydroalkoxylation and hydroamination of unactivated alkenes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yali Zhou ◽  
Xingjun Xu ◽  
Hongwei Sun ◽  
Guanyu Tao ◽  
Xiao-Yong Chang ◽  
...  
Keyword(s):  
Catalytic System ◽  
Rational Design ◽  
Platinum Catalysts ◽  
High Reactivity ◽  
Structural Components ◽  
Mechanistic Studies ◽  
Mild Conditions ◽  
Naturally Occurring ◽  
Donor Acceptor ◽  
Type Intermediate

AbstractHydrofunctionalization, the direct addition of an X–H (e.g., X=O, N) bond across an alkene, is a desirable strategy to make heterocycles that are important structural components of naturally occurring molecules. Described here is the design and discovery of “donor–acceptor”-type platinum catalysts that are highly effective in both hydroalkoxylation and hydroamination of unactivated alkenes over a broad range of substrates under mild conditions. A number of alkene substitution patterns are accommodated, including tri-substituted, 1,1-disubstituted, (E)-disubstituted, (Z)-disubstituted and even mono-substituted double bonds. Detailed mechanistic investigations suggest a plausible pathway that includes an unexpected dissociation/re-association of the electron-deficient ligand to form an alkene-bound “donor–acceptor”-type intermediate. These mechanistic studies help understand the origins of the high reactivity exhibited by the catalytic system, and provide a foundation for the rational design of chiral catalysts towards asymmetric hydrofunctionalization reactions.

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