Microbial cell factories have been widely used in the production of various chemicals. Although synthetic biology is useful in improving the cell factories, adaptation is still widely applied to enhance its complex properties. Adaptation is an important strategy for enhancing stress tolerance in microbial cell factories. Adaptation involves gradual modifications of microorganisms in a stressful environment to enhance their tolerance. During adaptation, microorganisms use different mechanisms to enhance non-preferred substrate utilization and stress tolerance, thereby improving their ability to adapt for growth and survival. In this paper, the progress on the effects of adaptation on microbial substrate utilization capacity and environmental stress tolerance are reviewed, and the mechanisms involved in enhancing microbial adaptive capacity are discussed.

A biological funnel pathway was established for the production of protocatechuic acid from lignin in engineered Saccharomyces cerevisiae.

Background As the second most abundant polysaccharide in nature, hemicellulose can be degraded to xylose as the feedstock for bioconversion to fuels and chemicals. To enhance xylose conversion, the engineered Saccharomyces cerevisiae with xylose metabolic pathway is usually adapted with xylose as the carbon source in the laboratory. However, the mechanism under the adaptation phenomena of the engineered strain is still unclear. Results In this study, xylose-utilizing S. cerevisiae was constructed and used for the adaptation study. It was found that xylose consumption rate increased 1.24-fold in the second incubation of the yYST12 strain in synthetic complete-xylose medium compared with the first incubation. The study figured out that it was observed at the single-cell level that the stagnation time for xylose utilization was reduced after adaptation with xylose medium in the microfluidic device. Such transient memory of xylose metabolism after adaptation with xylose medium, named “xylose consumption memory”, was observed in the strains with both xylose isomerase pathway and xylose reductase and xylitol dehydrogenase pathways. In further, the proteomic acetylation of the strains before and after adaptation was investigated, and it was revealed that H4K5 was one of the most differential acetylation sites related to xylose consumption memory of engineered S. cerevisiae. We tested 8 genes encoding acetylase or deacetylase, and it was found that the knockout of the GCN5 and HPA2 encoding acetylases enhanced the xylose consumption memory. Conclusions The behavior of xylose consumption memory in engineered S. cerevisiae can be successfully induced with xylose in the adaptation. H4K5Ac and two genes of GCN5 and HPA2 are related to xylose consumption memory of engineered S. cerevisiae during adaptation. This study provides valuable insights into the xylose adaptation of engineered S. cerevisiae.

Background Lignocellulosic biomass upgrading has become a promising alternative route to produce transportation fuels in response to energy security and environmental concerns. As the second most abundant polysaccharide in nature, hemicellulose mainly containing xylose is an important carbon source that can be used for the bioconversion to fuels and chemicals. However, the adaptation phenomena could appear and influence the bioconversion performance of xylose when Saccharomyces cerevisiae strain was transferred from the glucose to the xylose environment. Therefore, it is crucial to elucidate the mechanism of this adaptation phenomena, which can guide the strategy exploration to improve the efficiency of xylose utilization. Results In this study, xylose-utilizing strains had been constructed to effectively consume xylose. It is found that the second incubation of yYST218 strain in synthetic complete-xylose medium resulted in a 1.24-fold increase in xylose consumption ability as compared with the first incubation in synthetic complete-xylose medium. The results clearly showed that growing S. cerevisiae again in synthetic complete-xylose medium can significantly reduce the stagnation time and thus achieved a faster growth rate, by comparing the growth status of the strain in synthetic complete-xylose medium for the first and second time at the single-cell level through Microfluidic technology. Although these xylose-utilizing strains possessed different xylose metabolism pathways, they exhibited the “transient memory” phenomenon of xylose metabolism after changing the culture environment to synthetic complete-xylose medium, which named ‘xylose consumption memory (XCM)’ of S. cerevisiae in this study. According to the identification of protein acetylation, partial least squares analysis and the confirmatory test had verified that H4K5Ac affected the state of “XCM” in S. cerevisiae. Knockout of the acetylase-encoding genes GCN5 and HPA2 enhanced the “XCM” of the strain. Protein acetylation analysis suggested that xylose induced perturbation in S. cerevisiae stimulated the rapid adaptation of strains to xylose environment by regulating the level of acetylation. Conclusions All these results indicated protein acetylation modification is an important aspect that protein acetylation regulated the state of “XCM” in S. cerevisiae and thus determine the environmental adaptation of S. cerevisiae. Systematically exploiting the regulation approach of protein acetylation in S. cerevisiae could provide valuable insights into the adaptation phenomena of microorganisms in complex industrial environments.