Metabolomic Studies Of Microbes During Industrial Ethanol And Penicillin Bioprocesses

In large-scale fermentation process, cells behaviour and producing characters areclosely related with the environment factors. The behaviours of cells in environmentresponse are a process of involved in transcription, protein metabolism and interactioncomplex, multi-level network system based on biochemical reaction and mass transfer.Traditional research methods and tools are difficulty to fully reveal its regularity. Inthis paper, we choose ethanol and penicillin of industrial biological processes forstudy systems. From the point of phospholipids and metabolomics, we systematicallycompare and analyse the differences of the microbial cells in different industrialmodels and different industrial scales. We try to get a better understanding of cellsbehaviour to the complex industrial environment in different industrial models anddifferent industrial scales on molecular level and provide a scientific basis foroptimizing and amplificating the bio-process.First, choosing the batch process and continuous process in large-scale ethanolindustry as study system, we analyse the similarities and differences of cells responsebehaviour of yeast fermentation patterns in different industry fermentation scales.Although, the trend of reducing sugar was similar in the two processes, the cellsviability and ethanol production in the pre-fermentation are significantly lower thanthese in continuous process. Metabolomics analysis shows that osmotic and oxidativestresses are two main environmental factors of causing yeast cells response behaviourdifferences between the two processes. In continuous per-fermentation process,massive accumulation of glycerol shows that high sugar concentration forms osmoticpressure. In hypersonic stimulation, glycerol accumulation adjusts cell osmoticpressure. In the later stage of batch fermentation process, the lactic acid accumulationshows that cellular oxidative stress is increasing. Different environmental stressresponse behaviour causes the differences of amino acid metabolism and TCA cyclemetabolic in the two processes. We further analyse the changes of cell phospholipidcomposition and content in the two processes. The synthetization of Phospholipid inLCUFA in industrial yeast shows the extension of Intracellular enzymes inpolyunsaturated fats, enzymes. The length changes of cellular phospholipid chain maybe an important response of yeast cells to complex industrial environment. Thecontents of PS and PG of LCUFA in batch process are higher than these in continuousprocess. In continuous process, the contents of intracellular phospholipid in LCUFAin early fermentation are higher than the other two stages and show a downward trend with the process of fermentation.Secondly, choosing penicillin processes in pilot and large-scale industrial processfor study, we analyse the expression differences in biomagnification in the industrialprocess of Penicillium chrysogenum intracellular small-molecule metabolism,phospholipid metabolism and secondary metabolism group comparatively andsystematically. We get a further research response process of penicillin chrysogenumin amplification process. Studies show that the early fermentation and mediumfermentation are critical for the accumulation of penicillin. In the industrialamplification process, penicillin production is closely related to intracellular aminoacid metabolism. In the medium fermentation, amino acid significantly accumulationpromotes the synthesis of penicillin. The results also show that Penicilliumchrysogenum glycolysis and TCA cycle paths have significantly different metaboliccharacteristics in different scales of penicillin fermentation. These differences arerelated to penicillin production and in the industrial amplification process thebiosynthesis of secondary metabolism is significantly influenced by primarymetabolism. In the early stage of pilot process, the primary metabolism of penicilliumchrysogenum is more active which leads to the rate reducing of penicillin synthesis inthe fermentation process. By comparing the differences of secondary metabolites indifferent scales of fermentation processes, we found that the mutual transformation ofsecondary metabolites and the influence of synthetic enzymes are the reasons ofcausing penicillin metabolic differences in industrial amplification process. Furtherstudies of phospholipid show that polyunsaturated phospholipids in the pilot processwere higher than that in industrial process. The changes of unsaturated phospholipidmolecules directly show the differences of mycelium patterns in fermentationprocesses. In the early pilot process, the high unsaturated reduces the cells viscosityand increases the rate of gas-liquid oxygen transfer which can promote more myceliliagrowth and also lead to the rate reducing of penicillin synthesis in fermentationprocess. Compared with pilot process, the industry process suffers heavierenvironmental stresses and cause mycelium divided. And in amplification process theenvironmental stress make for the increasing of penicillin production.