接合によりグルコアミラーゼ遺伝子STA1が発現したビール酵母の育種

Standard brewing yeast cannot utilize larger oligomers or dextrins, which represent about 25% of wort sugars. A brewing yeast strain that could ferment these additional sugars to ethanol would be useful for producing low-carbohydrate diabetic or low-calorie beers. In this study, a brewing yeast strain that secretes glucoamylase was constructed by mating. The resulting Saccharomyces cerevisiae 278/113371 yeast was MATa/ diploid, but expressed the glucoamylase gene STA1. At the early phase of the fermentation test in malt extract medium, the fermentation rate of the diploid STA1 strain was slower than those of both the parent strain S. cerevisiae MAFF113371 and the reference strain bottom-fermenting yeast Weihenstephan 34/70. At the later phase of the fermentation test, however, the fermentation rate of the STA1 yeast strain was faster than those of the other strains. The concentration of ethanol in the culture supernatant of the STA1 yeast strain after the fermentation test was higher than those of the others. The concentration of all maltooligosaccharides in the culture supernatant of the STA1 yeast strain after the fermentation test was lower than those of the parent and reference strains, whereas the concentrations of flavor compounds in the culture supernatant were higher. These effects are due to the glucoamylase secreted by the constructed STA1 yeast strain. In summary, a glucoamylase-secreting diploid yeast has been constructed by mating that will be useful for producing novel types of beer owing to its different fermentation pattern and concentrations of ethanol and flavor compound

味噌醤油酵母Zygosaccharomyces酵母の接合遺伝子座(mating-type-like (MTL) loci)の多様性

Variations of chromosomal structures and nucleotide sequences around mating-type-like (MTL) loci among Zygosaccharomyces species have been reported. We have analyzed these differences in more detail and, on the basis of PCR- and next-generation sequencing data, we describe the MTL loci on chromosomes C and F for Z. rouxii type-strain NBRC1130, Z. rouxii NBRC0740 and Zygosaccharomyces sp. NBRC1876. We developed a mating strategy for Zygosaccharomyces sp. NBRC1876 and Z. rouxii NBRC0740, and found that the mated stains could be identified from parental strains on the basis of nucleotide sequence variations of the MTL loci. We further obtained evidence that Zygosaccharomyces sp. NBRC1876 is a natural interspecies hybrid between Z. rouxii and a related species

マルトース発酵関連遺伝子のクローニング

Maltose fermentation activator protein, MAL63homologue, MAL63 (NCYC1006), was clone from S. cerevisiaeNCYC1006. This yeast strain is top-fermenting yeast, and ferments maltose very well. Laboratory yeast S. cerevisiaeYNN27 could not ferment maltose very well, however, the transformant with MAL63 (NCYC1006) could ferment maltose very well. MAL63 (NCYC1006) has zinc-finger motif, which is transcriptional activation motif. It is inferred that MAL63 (NCYC1006) is located on chromosome VII. There are variations of maltose fermenting gene family among inter-Saccharomyces strains and intra-Saccharomyces strain genomes

マルトース発酵関連遺伝子のクローニングと染色体位置の決定（第２報）

Maltose fermentation activator protein, MAL63 homologue, MAL63 (NCYC1006), was cloned from S. cerevisiae NCYC1006. This yeast strain is top-fermenting yeast, and ferments maltose very well. Laboratory yeast S. cerevisiae YNN27 ferments maltose very poorly, however, the transformant with MAL63 (NCYC1006) could ferment maltose very well. Genome sequencing by a next generation sequencer revealed the chromosomal location of MAL63 (NCYC1006). These typical chromosomal structures are conserved among top-fermenting yeast strains and bottom-fermenting yeast strain

地方清酒製造に貢献できる清酒酵母の育種

In order to contribute regional sake production, we have been trying to isolate yeast strains from nature. Yeast strain MITOY20 had a good sake fermentation performance compared to sake yeast strain K701. The meiotic segregant MITOY66 which exhibited mating type a was isolated from sake yeast K701 which was treated with rapamycin

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target