Acetic acid accumulation is a universal limiting factor to the vinegar manufacture because of the toxic effect of acetic acid on the acid producing strain, such as Acetobacter pasteurianus. In this study, we aimed to investigate the genome-wide transcriptional response of A. pasteurianus Ab3 to high acid stress during vinegar production. By comparing the transcriptional landscape of cells harvested from a long-term cultivation with high acidity (70 ± 3 g/L) to that of low acidity (10 ± 2 g/L), we demonstrated that 1005 genes were differentially expressed. By functional enrichment analysis, we found that the expression of genes related to the two-component systems (TCS) and toxin-antitoxin systems (TAS) was significantly regulated under high acid stress. Cells increased the genome stability to withstand the intracellular toxicity caused by the acetic acid accumulation by repressing the expression of transposases and integrases. Moreover, high acid stress induced the expression of genes involved in the pathways of peptidoglycan, ceramide, and phosphatidylcholine biosynthesis as well as the Tol-Pal and TonB-ExbB systems. In addition, we observed that cells increased and diversified the ATP production to resist high acid stress. Transcriptional upregulation in the pathways of pyrroloquinoline quinone (PQQ) synthesis and thiamine metabolism suggested that cells may increase the production of prosthetic groups to ensure the enzyme activity upon high acid stress. Collectively, the results of this study increase our current understanding of the acetic acid resistance (AAR) mechanisms in A. pasteurianus and provide opportunities for strain improvement and scaled-up vinegar production.

Key Points

• TCS and TAS are responsive to the acid stress and constitute the regulating networks.

• Adaptive expression changes of cell envelope elements help cell resist acid stress.

• Cells promote genome stability and diversify ATP production to withstand acid stress.

乙酸的积累是醋生产的普遍限制因素，因为乙酸对产酸菌株（如巴氏醋杆菌）有毒作用。在这项研究中，我们旨在调查巴氏曲霉的全基因组转录反应。在醋生产过程中，Ab3对高酸胁迫。通过比较长期培养的高酸度（70±3 g / L）与低酸度（10±2 g / L）收获的细胞的转录情况，我们证明了1005个基因的差异表达。通过功能富集分析，我们发现与双组分系统（TCS）和毒素-抗毒素系统（TAS）相关的基因的表达在高酸胁迫下受到显着调节。细胞通过抑制转座酶和整合酶的表达，提高了基因组的稳定性，以承受由乙酸积累引起的细胞内毒性。此外，高酸胁迫诱导了参与肽聚糖，神经酰胺和磷脂酰胆碱生物合成以及Tol-Pal和TonB-ExbB系统途径的基因表达。此外，我们观察到细胞可以增加和多样化ATP的产生，以抵抗高酸胁迫。吡咯并喹啉醌（PQQ）合成和硫胺素代谢途径中的转录上调提示细胞可增加假体基团的产生，以确保在高酸胁迫下酶的活性。总的来说，这项研究的结果增加了我们目前对乙酸抗性（AAR）机理的了解。巴氏杆菌，并提供了改善菌株和扩大醋产量的机会。

关键点

• TCS和TAS对酸胁迫有反应并构成调节网络。

•细胞包膜元件的自适应表达变化有助于细胞抵抗酸胁迫。

•细胞促进基因组稳定性，并使ATP产生多样化，以抵抗酸胁迫。