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Nicotinic acid availability impacts redox cofactor metabolism in Saccharomyces cerevisiae during alcoholic fermentation 烟酸可用性影响酿酒酵母在酒精发酵过程中的氧化还原辅因子代谢
IF 3.2 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-04-18 DOI: 10.1093/femsyr/foae015
James D Duncan, Mathabatha E Setati, Benoit Divol
Anaerobic alcoholic fermentation, particularly in high-sugar environments, presents metabolic challenges for yeasts. Crabtree-positive yeasts, including Saccharomyces cerevisiae, prefer fermentation even in the presence of oxygen. These yeasts rely on internal NAD+ recycling and extracellular assimilation of its precursor, nicotinic acid (vitamin B3), rather than de novo NAD+ production. Surprisingly, nicotinic acid assimilation is poorly characterised, even in S. cerevisiae. This study elucidated the timing of nicotinic acid uptake during grape juice-like fermentation and its impact on NAD(H) levels, the NAD+/NADH ratio, and metabolites produced. Complete uptake of extracellular nicotinic acid occurred pre-mid-exponential phase, thereafter small amounts of vitamin B3 were exported back into the medium. Suboptimal levels of nicotinic acid were correlated with slower fermentation and reduced biomass, disrupting redox balance and impeding NAD+ regeneration, thereby affecting metabolite production. Metabolic outcomes varied with nicotinic acid concentrations, linking NAD+ availability to fermentation efficiency. A model was proposed encompassing rapid nicotinic acid uptake, accumulation during cell proliferation, and recycling with limited vitamin B3 export. This research enhances the understanding of nicotinic acid uptake dynamics during grape juice-like fermentation. These insights contribute to advancing yeast metabolism research and have profound implications for the enhancement of biotechnological practices and the winemaking industry.
厌氧酒精发酵,尤其是在高糖环境中,给酵母菌的新陈代谢带来了挑战。包括酿酒酵母(Saccharomyces cerevisiae)在内的克拉布特里阳性酵母即使在有氧的情况下也喜欢发酵。这些酵母依靠内部 NAD+ 循环和细胞外同化其前体烟酸(维生素 B3),而不是从头生产 NAD+。令人惊讶的是,即使在麦角菌中,烟酸的同化作用也鲜为人知。本研究阐明了葡萄汁类发酵过程中烟酸吸收的时间及其对 NAD(H)水平、NAD+/NADH 比率和代谢产物产生的影响。细胞外烟酸的完全吸收发生在爆发期中期之前,之后少量维生素 B3 被输出回培养基中。烟酸水平不足与发酵速度减慢和生物量减少有关,会破坏氧化还原平衡,阻碍 NAD+ 的再生,从而影响代谢物的产生。代谢结果随烟酸浓度的变化而变化,从而将 NAD+ 的可用性与发酵效率联系起来。研究提出了一个模型,包括烟酸的快速吸收、细胞增殖过程中的积累以及维生素 B3 的有限输出循环。这项研究加深了人们对葡萄汁类发酵过程中烟酸摄取动态的理解。这些见解有助于推进酵母新陈代谢研究,对提高生物技术实践和酿酒业具有深远影响。
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引用次数: 0
Enhancing xylose fermentation capacity of engineered Saccharomyces cerevisiae by multi-step evolutionary engineering in inhibitor-rich lignocellulose hydrolysate 在富含抑制剂的木质纤维素水解物中,通过多步进化工程提高工程酿酒酵母的木糖发酵能力
IF 3.2 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-04-10 DOI: 10.1093/femsyr/foae013
Mekonnen M Demeke, Dannele Echemendia, Edgard Belo, María R Foulquié-Moreno, Johan M Thevelein
Major progress in developing Saccharomyces cerevisiae strains that utilize the pentose sugar xylose has been achieved. However, the high inhibitor content of lignocellulose hydrolysates still hinders efficient xylose fermentation, which remains a major obstacle for commercially viable second-generation bioethanol production. Further improvement of xylose utilization in inhibitor-rich lignocellulose hydrolysates remains highly challenging. In this work, we have developed a robust industrial S. cerevisiae strain able to efficiently ferment xylose in concentrated undetoxified lignocellulose hydrolysates. This was accomplished with novel multi-step evolutionary engineering. First, a tetraploid strain was generated and evolved in xylose-enriched pretreated spruce biomass. The best evolved strain was sporulated to obtain a genetically diverse diploid population. The diploid strains were then screened in industrially relevant conditions. The best performing strain, MDS130, showed superior fermentation performance in three different lignocellulose hydrolysates. In concentrated corncob hydrolysate, with initial cell density of 1 g DW/L, at 35°C, MDS130 completely co-consumed glucose and xylose, producing ± 7% v/v ethanol with a yield of 91% of the maximum theoretical value and an overall productivity of 1.22 g/L/h. MDS130 has been developed from previous industrial yeast strains without applying external mutagenesis, minimizing the risk of negative side-effects on other commercially important properties and maximizing its potential for industrial application.
在开发可利用戊糖木糖的酿酒酵母菌株方面取得了重大进展。然而,木质纤维素水解物中的高抑制剂含量仍然阻碍着木糖的高效发酵,这仍然是商业上可行的第二代生物乙醇生产的主要障碍。进一步提高木糖在富含抑制剂的木质纤维素水解物中的利用率仍然极具挑战性。在这项工作中,我们开发出了一种强健的工业 S. cerevisiae 菌株,能够在浓缩的未解毒木质纤维素水解物中高效发酵木糖。这是通过新颖的多步骤进化工程实现的。首先,生成四倍体菌株,并在富含木糖的预处理云杉生物质中进行进化。对进化出的最佳菌株进行孢子培养,以获得基因多样化的二倍体群体。然后在工业相关条件下对二倍体菌株进行筛选。表现最好的菌株 MDS130 在三种不同的木质纤维素水解物中都表现出卓越的发酵性能。在浓缩玉米芯水解物中,初始细胞密度为 1 g DW/L,在 35°C 温度下,MDS130 完全共消耗葡萄糖和木糖,产生 ± 7% v/v 的乙醇,产量为最大理论值的 91%,总生产率为 1.22 g/L/h。MDS130 是在以前的工业酵母菌株基础上开发出来的,没有进行外部诱变,从而最大限度地降低了对其他重要商业特性产生负面副作用的风险,并最大限度地提高了其工业应用潜力。
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引用次数: 0
Mitochondria complex I deficiency in Candida albicans arrests the cell cycle at S phase through suppressive TOR and PKA pathways 白色念珠菌线粒体复合体 I 缺乏可通过抑制性 TOR 和 PKA 途径使细胞周期停滞在 S 期
IF 3.2 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-04-09 DOI: 10.1093/femsyr/foae010
Lulu Zhang, Zhou Meng, Richard Calderone, Weida Liu, Xiaodong She, Dongmei Li
How mutations in mitochondrial electron transport chain (ETC) proteins impact the cell cycle of Candida albicans was investigated in this study. Using genetic null mutants targeting ETC complexes I (CI), III (CIII), and IV (CIV), the cell cycle stages (G0/G1, S-phase, and G2/M) were analyzed via fluorescence-activated cell sorting (FACS). Four CI null mutants exhibited distinct alterations, including extended S- phase, shortened G2/M population and a reduction in cells size exceeding 10 μM. Conversely, CIII mutants showed an increased population in G1/G0 phase. Among four CI mutants, ndh51Δ/Δ and goa1Δ/Δ displayed aberrant cell cycle patterns correlated with previously reported cAMP/PKA downregulation. Specifically, nuo1Δ/Δ and nuo2Δ/Δ mutants exhibited increased transcription of RIM15, a central hub linking cell cycle with nutrient-dependent TOR1 and cAMP/PKA pathways and Snf1 aging pathway. These findings suggest that suppression of TOR1 and cAMP/PKA pathways or enhanced Snf1 disrupts cell cycle progression, influencing cell longevity and growth among CI mutants. Overall, our study highlights the intricate interplay between mitochondrial ETC, cell cycle, and signaling pathways.
本研究调查了线粒体电子传递链(ETC)蛋白的突变如何影响白色念珠菌的细胞周期。利用针对 ETC 复合物 I(CI)、III(CIII)和 IV(CIV)的基因空突变体,通过荧光激活细胞分拣(FACS)分析了细胞周期阶段(G0/G1、S 期和 G2/M)。四个 CI 空突变体表现出明显的变化,包括 S 期延长、G2/M 群体缩短以及细胞体积缩小超过 10 μM。相反,CIII突变体在G1/G0期的细胞数量增加。在四个CI突变体中,ndh51Δ/Δ和goa1Δ/Δ显示出与先前报道的cAMP/PKA下调相关的异常细胞周期模式。具体来说,nuo1Δ/Δ 和 nuo2Δ/Δ 突变体的 RIM15 转录增加,RIM15 是连接细胞周期与营养依赖性 TOR1 和 cAMP/PKA 通路以及 Snf1 衰老通路的中心枢纽。这些发现表明,TOR1 和 cAMP/PKA 通路的抑制或 Snf1 的增强会扰乱细胞周期的进展,从而影响 CI 突变体的细胞寿命和生长。总之,我们的研究强调了线粒体 ETC、细胞周期和信号通路之间错综复杂的相互作用。
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引用次数: 0
Mitochondrial membrane transporters as attractive targets for the fermentative production of succinic acid from glycerol in Saccharomyces cerevisiae 线粒体膜转运体是酿酒酵母发酵生产甘油琥珀酸的诱人靶标
IF 3.2 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-04-08 DOI: 10.1093/femsyr/foae009
Toni Rendulić, Andreea Perpelea, Juan Paulo Ragas Ortiz, Margarida Casal, Elke Nevoigt
Previously, we reported an engineered Saccharomyces cerevisiae CEN.PK113-1A derivative able to produce succinic acid (SA) from glycerol with net CO2 fixation. Apart from an engineered glycerol utilization pathway, the strain was equipped with the reductive branch of the TCA cycle (rTCA) and a heterologous SA exporter. However, the results indicated that a significant amount of carbon still entered the CO2-releasing oxidative TCA cycle. The current study aimed to tune down the flux through the oxidative TCA cycle by targeting the mitochondrial uptake of pyruvate and cytosolic intermediates of the rTCA pathway, as well as the succinate dehydrogenase complex. Thus, we tested the effects of deletions of MPC1, MPC3, OAC1, DIC1, SFC1, and SDH1 on SA production. The highest improvement was achieved by the combined deletion of MPC3 and SDH1. The respective strain produced up to 45.5 g/L of SA, reached a maximum SA yield of 0.66 gSA/gglycerol, and accumulated the lowest amounts of byproducts. Based on the obtained data, we consider a further reduction of mitochondrial import of pyruvate and rTCA intermediates highly attractive. Moreover, the approaches presented in the current study might also be valuable for improving SA production when sugars (instead of glycerol) are the source of carbon.
此前,我们报道了一种工程化的酿酒酵母 CEN.PK113-1A 衍生物,它能够利用甘油生产琥珀酸(SA),并具有净二氧化碳固定能力。除了改造甘油利用途径外,该菌株还配备了 TCA 循环的还原分支(rTCA)和异源 SA 导出器。然而,研究结果表明,仍有大量碳进入释放二氧化碳的氧化 TCA 循环。目前的研究旨在通过靶向丙酮酸的线粒体摄取和 rTCA 途径的细胞膜中间产物以及琥珀酸脱氢酶复合物来降低通过氧化 TCA 循环的通量。因此,我们测试了缺失 MPC1、MPC3、OAC1、DIC1、SFC1 和 SDH1 对 SA 产量的影响。MPC3和SDH1的联合缺失对SA产量的提高最大。该菌株的 SA 产量高达 45.5 克/升,最大 SA 产量为 0.66 克/克甘油,副产物积累量最低。根据所获得的数据,我们认为进一步减少线粒体丙酮酸和 rTCA 中间产物的输入极具吸引力。此外,当糖(而不是甘油)作为碳源时,本研究提出的方法可能对提高 SA 的产量也很有价值。
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引用次数: 0
Maltose accumulation induced cell death in Saccharomyces cerevisiae 麦芽糖积累诱导酿酒酵母细胞死亡
IF 3.2 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-04-01 DOI: 10.1093/femsyr/foae012
Xiaohuan Zhang, Jeroen G Nijland, Arnold J M Driessen
Pretreatment of lignocellulose yields a complex sugar mixture that potentially can be converted into bioethanol and other chemicals by engineered yeast. One approach to overcome competition between sugars for uptake and metabolism is the use of a consortium of specialist strains capable of efficient conversion of single sugars. Here we show that maltose inhibits cell growth of a xylose-fermenting specialist strain IMX730.1 that is unable to utilize glucose because of the deletion of all hexokinase genes. The growth inhibition cannot be attributed to a competition between maltose and xylose for uptake. The inhibition is enhanced in a strain lacking maltase enzymes (dMalX2) and completely eliminated when all maltose transporters are deleted. High-level accumulation of maltose in the dMalX2 strain is accompanied by a hypotonic-like transcriptional response, while cells are rescued from maltose-induced cell death by the inclusion of an extracellular osmolyte such as sorbitol. These data suggest that maltose-induced cell death is due to high levels of maltose uptake causing hypotonic-like stress conditions and can be prevented through engineering of the maltose transporters. Transporter engineering should be included in the development of stable microbial consortia for the efficient conversion of lignocellulosic feedstocks.
木质纤维素的预处理会产生一种复杂的糖混合物,这种混合物有可能被工程酵母转化为生物乙醇和其他化学品。克服糖类之间吸收和代谢竞争的一种方法是使用能够高效转化单糖的专一菌株联合体。在这里,我们发现麦芽糖抑制了木糖发酵专性菌株 IMX730.1 的细胞生长,该菌株由于缺失了所有己糖激酶基因而无法利用葡萄糖。生长抑制不能归因于麦芽糖和木糖之间的吸收竞争。在缺乏麦芽糖酶的菌株(dMalX2)中,这种抑制作用会增强,而在删除所有麦芽糖转运体后,这种抑制作用会完全消失。在 dMalX2 菌株中,麦芽糖的高水平积累伴随着低渗样转录反应,而细胞在加入山梨醇等细胞外渗透溶质后可从麦芽糖诱导的细胞死亡中解救出来。这些数据表明,麦芽糖诱导的细胞死亡是由于高水平的麦芽糖摄取导致低张性应激条件造成的,可以通过麦芽糖转运体工程来防止。在开发稳定的微生物联合体以高效转化木质纤维素原料的过程中,应包括转运体工程。
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引用次数: 0
Natural trait variation across Saccharomycotina species 酵母菌物种间的天然性状变异
IF 3.2 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-01-13 DOI: 10.1093/femsyr/foae002
Johnson J-T Wang, Jacob L Steenwyk, Rachel B Brem
Among molecular biologists, the group of fungi called Saccharomycotina is famous for its yeasts. These yeasts in turn are famous for what they have in common—genetic, biochemical, and cell-biological characters that serve as models for plants and animals. But behind the apparent homogeneity of Saccharomycotina species lie a wealth of differences. In this review, we discuss traits that vary across the Saccharomycotina subphylum. We describe cases of bright pigmentation; a zoo of cell shapes; metabolic specialties; and species with unique rules of gene regulation. We discuss the genetics of this diversity and why it matters, including insights into basic evolutionary principles with relevance across Eukarya.
在分子生物学家中,被称为酵母菌纲(Saccharomycotina)的真菌类群因其酵母菌而闻名。这些酵母菌又因其共同点--遗传、生化和细胞生物学特征而闻名,可作为动植物的模型。但是,在酵母菌物种表面同质化的背后,却隐藏着大量的差异。在这篇综述中,我们将讨论酵母菌亚门的不同特征。我们描述了亮色素沉着、细胞形状动物园、代谢特长以及具有独特基因调控规则的物种。我们讨论了这种多样性的遗传学及其重要原因,包括对与真核生物相关的基本进化原理的见解。
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引用次数: 0
The cell morphological diversity of Saccharomycotina yeasts. 酵母菌的细胞形态多样性。
IF 2.4 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-01-09 DOI: 10.1093/femsyr/foad055
Christina M Chavez, Marizeth Groenewald, Amanda B Hulfachor, Gideon Kpurubu, Rene Huerta, Chris Todd Hittinger, Antonis Rokas

The ∼1 200 known species in subphylum Saccharomycotina are a highly diverse clade of unicellular fungi. During its lifecycle, a typical yeast exhibits multiple cell types with various morphologies; these morphologies vary across Saccharomycotina species. Here, we synthesize the evolutionary dimensions of variation in cellular morphology of yeasts across the subphylum, focusing on variation in cell shape, cell size, type of budding, and filament production. Examination of 332 representative species across the subphylum revealed that the most common budding cell shapes are ovoid, spherical, and ellipsoidal, and that their average length and width is 5.6 µm and 3.6 µm, respectively. 58.4% of yeast species examined can produce filamentous cells, and 87.3% of species reproduce asexually by multilateral budding, which does not require utilization of cell polarity for mitosis. Interestingly, ∼1.8% of species examined have not been observed to produce budding cells, but rather only produce filaments of septate hyphae and/or pseudohyphae. 76.9% of yeast species examined have sexual cycle descriptions, with most producing one to four ascospores that are most commonly hat-shaped (37.4%). Systematic description of yeast cellular morphological diversity and reconstruction of its evolution promises to enrich our understanding of the evolutionary cell biology of this major fungal lineage.

酵母菌亚门(Saccharomycotina)中的 1200 个已知物种是一个高度多样化的单细胞真菌支系。在其生命周期中,典型的酵母菌表现出多种形态的细胞类型;这些形态在酵母菌亚门的不同物种中也各不相同。在这里,我们综合分析了酵母菌亚门中细胞形态变异的进化层面,重点研究了细胞形状、细胞大小、出芽类型和菌丝产生等方面的变异。对亚门中 332 个代表性物种的研究表明,最常见的芽胞形状是卵圆形、球形和椭圆形,其平均长度和宽度分别为 5.6 μm 和 3.6 μm。58.4%的酵母菌能产生丝状细胞,87.3%的酵母菌通过多边出芽进行无性繁殖,这不需要利用细胞极性进行有丝分裂。有趣的是,有 1.8%的酵母菌种不能产生出芽细胞,而只能产生丝状的隔膜菌丝和/或假菌丝。76.9% 的受检酵母菌种有有性生殖周期的描述,其中大多数会产生一到四个最常见的帽子形(37.4%)的腹孢子。对酵母细胞形态多样性的系统描述及其进化重建有望丰富我们对这一主要真菌品系细胞生物学进化的认识。
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引用次数: 0
Diacylglycerol metabolism and homeostasis in fungal physiology. 真菌生理学中的二酰基甘油代谢和体内平衡。
IF 2.4 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-01-09 DOI: 10.1093/femsyr/foae036
Sudipta Mondal, Biswajit Pal, Rajan Sankaranarayanan

Diacylglycerol (DAG) is a relatively simple and primitive form of lipid, which does not possess a phospholipid headgroup. Being a central metabolite of the lipid metabolism network, DAGs are omnipresent in all life forms. While the role of DAG has been established in membrane and storage lipid biogenesis, it can impart crucial physiological functions including membrane shapeshifting, regulation of membrane protein activity, and transduction of cellular signalling as a lipid-based secondary messenger. Besides, the chemical diversity of DAGs, due to fatty acyl chain composition, has been proposed to be the basis of its functional diversity. Therefore, cells must regulate DAG level at a spatio-temporal scale for homeostasis and adaptation. The vast network of eukaryotic lipid metabolism has been unravelled majorly by studying yeast models. Here, we review the current understanding and the emerging concepts in metabolic and functional aspects of DAG regulation in yeast. The implications can be extended to understand pathogenic fungi and mammalian counterparts as well as disease aetiology.

二酰基甘油(DAG)是一种相对简单和原始的脂质形式,它不具有磷脂头基。作为脂质代谢网络的中心代谢物,dag在所有生命形式中无处不在。虽然DAG在膜和储存脂质生物发生中的作用已经确立,但它可以作为基于脂质的次级信使,赋予重要的生理功能,包括膜形状改变,膜蛋白活性调节和细胞信号转导。此外,由于脂肪酸酰基链的组成,DAGs的化学多样性被认为是其功能多样性的基础。因此,细胞必须在时空尺度上调节DAG水平,以实现体内平衡和适应。真核生物脂质代谢的庞大网络主要是通过研究酵母模型来揭示的。在这里,我们回顾了目前的理解和新兴的概念在代谢和功能方面的DAG调控酵母。其含义可以扩展到了解病原真菌和哺乳动物的对应物以及疾病病原学。
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引用次数: 0
Increased production of isobutanol from xylose through metabolic engineering of Saccharomyces cerevisiae overexpressing transcription factor Znf1 and exogenous genes. 通过过度表达转录因子 Znf1 和外源基因的酿酒酵母代谢工程提高木糖异丁醇的产量。
IF 2.4 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-01-09 DOI: 10.1093/femsyr/foae006
Pattanan Songdech, Chutikarn Butkinaree, Yodying Yingchutrakul, Peerada Promdonkoy, Weerawat Runguphan, Nitnipa Soontorngun

Only trace amount of isobutanol is produced by the native Saccharomyces cerevisiae via degradation of amino acids. Despite several attempts using engineered yeast strains expressing exogenous genes, catabolite repression of glucose must be maintained together with high activity of downstream enzymes, involving iron-sulfur assimilation and isobutanol production. Here, we examined novel roles of nonfermentable carbon transcription factor Znf1 in isobutanol production during xylose utilization. RNA-seq analysis showed that Znf1 activates genes in valine biosynthesis, Ehrlich pathway and iron-sulfur assimilation while coupled deletion or downregulated expression of BUD21 further increased isobutanol biosynthesis from xylose. Overexpression of ZNF1 and xylose-reductase/dehydrogenase (XR-XDH) variants, a xylose-specific sugar transporter, xylulokinase, and enzymes of isobutanol pathway in the engineered S. cerevisiae pho13gre3Δ strain resulted in the superb ZNXISO strain, capable of producing high levels of isobutanol from xylose. The isobutanol titer of 14.809 ± 0.400 g/L was achieved, following addition of 0.05 g/L FeSO4.7H2O in 5 L bioreactor. It corresponded to 155.88 mg/g xylose consumed and + 264.75% improvement in isobutanol yield. This work highlights a new regulatory control of alternative carbon sources by Znf1 on various metabolic pathways. Importantly, we provide a foundational step toward more sustainable production of advanced biofuels from the second most abundant carbon source xylose.

原生的酿酒酵母只能通过氨基酸降解产生微量的异丁醇。尽管使用表达外源基因的工程酵母菌株进行了多次尝试,但葡萄糖的分解抑制必须与下游酶的高活性一起维持,其中涉及铁硫同化和异丁醇的生产。在此,我们研究了非发酵碳转录因子 Znf1 在木糖利用过程中产生异丁醇的新作用。RNA-seq分析表明,Znf1能激活缬氨酸生物合成、艾氏途径和铁硫同化作用中的基因,而BUD21的偶联缺失或下调表达能进一步提高木糖异丁醇的生物合成。在工程化的 S. cerevisiae pho13gre3Δ 菌株中过表达 ZNF1 和木糖还原酶/脱氢酶(XR-XDH)变体、木糖特异性糖转运体、木聚糖酶和异丁醇途径的酶,产生了极好的 ZNXISO 菌株,能够从木糖中产生高水平的异丁醇。在 5 L 生物反应器中加入 0.05 g/L FeSO4.7H2O 后,异丁醇滴度达到 14.809 ± 0.400 g/L。这相当于消耗了 155.88 毫克/克木糖,异丁醇产量提高了 + 264.75%。这项工作强调了 Znf1 对各种代谢途径的替代碳源的新调控。重要的是,我们为利用第二大丰富碳源木糖更可持续地生产高级生物燃料迈出了奠基性的一步。
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引用次数: 0
Regulation of copper uptake by the SWI/SNF chromatin remodeling complex in Candida albicans affects susceptibility to antifungal and oxidative stresses under hypoxia. 白念珠菌中 SWI/SNF 染色质重塑复合体对铜吸收的调控影响了在缺氧条件下对抗真菌和氧化应激的敏感性。
IF 2.4 4区 生物学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY Pub Date : 2024-01-09 DOI: 10.1093/femsyr/foae018
Inès Khemiri, Faiza Tebbji, Anaïs Burgain, Adnane Sellam

Candida albicans is a human colonizer and also an opportunistic yeast occupying different niches that are mostly hypoxic. While hypoxia is the prevalent condition within the host, the machinery that integrates oxygen status to tune the fitness of fungal pathogens remains poorly characterized. Here, we uncovered that Snf5, a subunit of the chromatin remodeling complex SWI/SNF, is required to tolerate antifungal stress particularly under hypoxia. RNA-seq profiling of snf5 mutant exposed to amphotericin B and fluconazole under hypoxic conditions uncovered a signature that is reminiscent of copper (Cu) starvation. We found that under hypoxic and Cu-starved environments, Snf5 is critical for preserving Cu homeostasis and the transcriptional modulation of the Cu regulon. Furthermore, snf5 exhibits elevated levels of reactive oxygen species and an increased sensitivity to oxidative stress principally under hypoxia. Supplementing growth medium with Cu or increasing gene dosage of the Cu transporter CTR1 alleviated snf5 growth defect and attenuated reactive oxygen species levels in response to antifungal challenge. Genetic interaction analysis suggests that Snf5 and the bona fide Cu homeostasis regulator Mac1 function in separate pathways. Together, our data underlined a unique role of SWI/SNF complex as a potent regulator of Cu metabolism and antifungal stress under hypoxia.

白色念珠菌是一种人类定植菌,也是一种机会性酵母菌,占据着不同的生境,这些生境大多缺氧。虽然缺氧是宿主体内的普遍状况,但整合氧气状态以调节真菌病原体适应性的机制仍然特征不清。在这里,我们发现染色质重塑复合物 SWI/SNF 的一个亚基 Snf5 是耐受抗真菌胁迫(尤其是在缺氧条件下)所必需的。在缺氧条件下,snf5突变体暴露于两性霉素B和氟康唑的RNA-seq图谱分析发现了一种与铜(Cu)饥饿相似的特征。我们发现,在缺氧和铜饥饿环境下,Snf5对维持铜平衡和铜调节子的转录调控至关重要。此外,Snf5主要在缺氧条件下表现出活性氧水平升高和对氧化应激的敏感性增强。在生长培养基中补充铜或增加铜转运体 CTR1 的基因剂量可减轻 snf5 的生长缺陷,并减轻 ROS 水平对抗真菌挑战的反应。基因相互作用分析表明,Snf5 和真正的铜平衡调节因子 Mac1 在不同的途径中发挥作用。总之,我们的数据强调了 SWI/SNF 复合物在缺氧条件下作为铜代谢和抗真菌胁迫强效调节因子的独特作用。
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FEMS yeast research
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