Myriocin-induced adaptive laboratory evolution of an industrial strain of Saccharomyces cerevisiae reveals its potential to remodel lipid composition and heat tolerance.,Microbial Biotechnology

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Myriocin-induced adaptive laboratory evolution of an industrial strain of Saccharomyces cerevisiae reveals its potential to remodel lipid composition and heat tolerance.
Microbial Biotechnology ( IF 4.8 ) Pub Date : 2020-03-25 , DOI: 10.1111/1751-7915.13555
Francisca Randez-Gil ₁ , Jose A Prieto ₁ , Alejandro Rodríguez-Puchades ₁ , Josefina Casas _{2,

3} , Vicente Sentandreu ₄ , Francisco Estruch ₅

Affiliation

The modification of lipid composition allows cells to adjust membrane biophysical properties in response to changes in environmental temperature. Here, we use adaptive laboratory evolution (ALE) in the presence of myriocin, a sphingolipid (SLs) biosynthesis inhibitor, to remodel the lipid profile of an industrial yeast strain (LH) of Saccharomyces cerevisiae. The approach enabled to obtain a heterogeneous population (LHev) of myriocin‐tolerant evolved clones characterized by its growth capacity at high temperature. Myriocin exposure also caused tolerance to soraphen A, an inhibitor of the acetyl‐CoA carboxylase Acc1, the rate‐limiting enzyme in fatty acid de novo production, supporting a change in lipid metabolism during ALE. In line with this, characterization of two randomly selected clones, LH03 and LH09, showed the presence of lipids with increased saturation degree and reduced acyl length. In addition, the clone LH03, which displays the greater improvement in fitness at 40°C, exhibited higher SL content as compared with the parental strain. Analysis of the LH03 and LH09 genomes revealed a loss of chromosomes affecting genes that have a role in fatty acid synthesis and elongation. The link between ploidy level and growth at high temperature was further supported by the analysis of a fully isogenic set of yeast strains with ploidy between 1N and 4N which showed that the loss of genome content provides heat tolerance. Consistent with this, a thermotolerant evolved population (LH40°) generated from the parental LH strain by heat‐driven ALE exhibited a reduction in the chromosome copy number. Thus, our results identify myriocin‐driven evolution as a powerful approach to investigate the mechanisms of acquired thermotolerance and to generate improved strains.

中文翻译：

多球菌素诱导的酿酒酵母工业菌株的适应性实验室进化揭示了其重塑脂质组成和耐热性的潜力。

脂质成分的改变使细胞能够根据环境温度的变化来调整膜的生物物理特性。在这里，我们在存在鞘脂 (SL) 生物合成抑制剂多球菌素的情况下使用适应性实验室进化 (ALE) 来重塑酿酒酵母工业酵母菌株 (LH) 的脂质谱。该方法能够获得耐多壳菌素进化克隆的异质群体（LHev），其特征在于其高温生长能力。多球菌素暴露还会引起对 soraphen A 的耐受性，soraphen A 是乙酰辅酶 A 羧化酶 Acc1 的抑制剂，是脂肪酸从头生产的限速酶，支持 ALE 期间脂质代谢的变化。与此相符，两个随机选择的克隆 LH03 和 LH09 的表征显示存在饱和度增加和酰基长度减少的脂质。此外，克隆LH03在40°C下表现出更大的适应性改善，与亲本菌株相比，表现出更高的SL含量。对 LH03 和 LH09 基因组的分析揭示了影响脂肪酸合成和延伸的基因的染色体丢失。对倍性在 1N 和 4N 之间的一组完全同基因酵母菌株的分析进一步支持了倍性水平与高温生长之间的联系，这表明基因组内容的损失提供了耐热性。与此相一致的是，通过热驱动 ALE 从亲本 LH 菌株产生的耐热进化群体 (LH40°) 表现出染色体拷贝数的减少。因此，我们的结果表明，多球菌素驱动的进化是研究获得性耐热性机制和产生改良菌株的有效方法。

更新日期：2020-03-25

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