Evolutionary engineering reveals divergent paths when yeast is adapted to different acidic environments
메타 데이터
바이오화학분류
바이오플라스틱
플라스틱
바이오정밀화학
용매
화학제품
연료
화장품용 기능성소재
계면활성제⁄증점제
의료용 화학소재
식품첨가제
논문
Evolutionary engineering reveals divergent paths when yeast is adapted to different acidic environments
학술지
Metabolic engineering
저자명
Fletcher, Eugene; Feizi, Amir; Bisschops, Markus M.M.; Hallströ m, Bjö rn M.; Khoomrung, Sakda; Siewers, Verena; Nielsen, Jens
초록
<P><B>Abstract</B></P> <P>Tolerance of yeast to acid stress is important for many industrial processes including organic acid production. Therefore, elucidating the molecular basis of long term adaptation to acidic environments will be beneficial for engineering production strains to thrive under such harsh conditions. Previous studies using gene expression analysis have suggested that both organic and inorganic acids display similar responses during short term exposure to acidic conditions. However, biological mechanisms that will lead to long term adaptation of yeast to acidic conditions remains unknown and whether these mechanisms will be similar for tolerance to both organic and inorganic acids is yet to be explored. We therefore evolved <I>Saccharomyces cerevisiae</I> to acquire tolerance to HCl (inorganic acid) and to 0.3M L-lactic acid (organic acid) at pH 2.8 and then isolated several low pH tolerant strains. Whole genome sequencing and RNA-seq analysis of the evolved strains revealed different sets of genome alterations suggesting a divergence in adaptation to these two acids. An altered sterol composition and impaired iron uptake contributed to HCl tolerance whereas the formation of a multicellular morphology and rapid lactate degradation was crucial for tolerance to high concentrations of lactic acid. Our findings highlight the contribution of both the selection pressure and nature of the acid as a driver for directing the evolutionary path towards tolerance to low pH. The choice of carbon source was also an important factor in the evolutionary process since cells evolved on two different carbon sources (raffinose and glucose) generated a different set of mutations in response to the presence of lactic acid. Therefore, different strategies are required for a rational design of low pH tolerant strains depending on the acid of interest.</P> <P><B>Highlights</B></P> <P> <UL> <LI> <I>Saccharomyces cerevisiae</I> was adapted to grow at low pH (2.8) and in high concentrations of L-lactic acid (0.3M). </LI> <LI> Divergent evolutionary paths were observed for tolerance to different acidic conditions. </LI> <LI> Reduced iron uptake and altered sterol composition was required for tolerance to an inorganic acid (HCl). </LI> <LI> Formation of multicellular structures and lactate degradation led to lactic acid tolerance. </LI> </UL> </P>