Insights into the response and tolerance mechanisms of Papiliotrema laurentii to acetic acid stress by RNA-seq and genome-scale metabolic modeling analysis

Abstract

Lipid production by oleaginous yeasts from lignocellulosic biomasses is a sustainable alternative to produce oleochemicals; nevertheless, the pretreatment of these biomasses releases yeast inhibitors, including acetic acid. Papiliotrema laurentii UFV-1 converts lignocelulose-derived sugars into high lipid contents; however, wild strains are sensitive to acetic acid. Previously, our group selected an acetic acid-tolerant strain of P. laurentii (ATS) by Adaptive Laboratory Evolution and identified mutations that might contribute to its tolerance. Here, we combined transcriptome, metabolic modeling and protein-protein interaction analyses to deepen our understanding about acetic acid stress targets and adaptive responses in P. laurentii. Acetic acid stress promoted global expression changes; most of them related to transcription, translation, and ribosome biogenesis. Under acetic acid stress, the sensitive strain induced DNA mismatch repair and meiosis, while the tolerant strain negatively regulated autophagy and cell cycle. The tolerant strain induced processes related to increasing intracellular pH, detoxification, and proton efflux. Importantly, ATS presented a remarkable NAD(P)H pool in the metabolic modeling analysis, which might support the reducing power required by tolerance mechanisms. Meanwhile, the sensitive strain induced genes related to cell wall biogenesis, consistent with its morphological changes described in our previous study. The pathways described as tolerant-related might be used in metabolic engineering strategies to improve the tolerance of P. laurentii to weak acids, boosting its application in lignocellulosic biorefineries.