Industrial bioprocess is a complex systematic process and bio-manufacturing can be realized on the basis of understanding the metabolism process of living cells. In this article, the multi-scale optimization principle and practice of industrial fermentation process are reviewed, including multi-scale optimizing theory and equipment, on-line sensing technology for cellular macroscopic metabolism, and correlated analysis of physiological parameters. Furthermore, intelligent control of industrial bioprocess is further addressed, in terms of new sensing technology for intracellular physiological metabolism, big database establishment and data depth calculation, intelligent decision.
Bioreactors ; Biotechnology ; Fermentation ; Industrial Microbiology

Industrial fermentation focuses on realizing the uniform of high titer, high yield, and high productivity. Multi-scale analysis and regulation, including molecule level, cell level, and bioreactor level, facilitate global optimization and dynamic balance of fermentation process, which determine high efficiency of biosynthesis, targeted directionality of bioconversion, process robustness, and well-organized system. In this review, we summariz and discuss advances in multi-scale analysis and regulation for fermentation process focusing on the following four aspects: 1) kinetic modeling of metabolic pathways, 2) characteristic of cell metabolism, 3) co-coupling fermentation and purification, and 4) bioreactor design. Integrating multi-scale analysis of fermentation process and integrating multi-scale regulation are expected as an important strategy for realizing highly efficient fermentation by industrial microorganisms.
Bioreactors ; Fermentation ; Industrial Microbiology ; Kinetics ; Metabolic Networks and Pathways

The production of propionic acid by Propionibacterium freudenreichii CCTCC M207015 was investigated in a Fibrous-bed bioreactor (FBB). The FBB was constructed by packing spiral cotton fibrous and immobilized into a bioreactor. By applying this bioreactor to propionic acid fermentation, the propionic acid yield had a significant improvement and reached 20.41 g/L, compared with the cell-free culture of 14.58 g/L (40 g/L of glucose). At the same time, the glucose exhausting time decreased from 120 h to 60 h. Batch fermentations at various glucose concentrations were carried out with FBB. Based on the analysis of the time course of production, fed-batch fermentation was also applied to produce propionic acid with FBB, the maximal propionic acid yield reached 45.91 g/L, and the proportion of propionic acid to total acids was about 72.31%.
Bioreactors ; microbiology ; Fermentation ; Glucose ; metabolism ; Propionates ; metabolism ; Propionibacterium ; classification ; metabolism

Prior research reported the oscillatory behavior characterized by long period and high amplitude during high gravity continuous ethanol fermentations at the dilution rate of 0.027 h(-1). In this paper, high gravity continuous ethanol fermentations using Saccharomyces cerevisia at different dilution rates were carried out. Similar oscillations were observed when the dilution rate was switched to 0.04 h(-1). Both oscillatory and steady processes can be achieved at dilution rates of 0.027 or 0.04 h(-1), which depends on the initial status of the fermentation system. However, compared to steady process at the same dilution rate of 0.04 h(-1), the average residual sugar concentration was lowered by 14.8% for the oscillatory process, while the average ethanol concentration and productivity were increased by 12.6% and 12.3%, respectively. Further investigation revealed that besides the lag time, oscillatory processes were different from steady ones in kinetics because a higher specific growth rate can be achieved at the same residual sugar and ethanol concentrations (increased by 53.8% in average).
Bioreactors ; microbiology ; Carbohydrates ; Ethanol ; metabolism ; Fermentation ; Hypergravity ; Saccharomyces cerevisiae ; metabolism

Alcohols ; metabolism ; Bioreactors ; microbiology ; History, 20th Century ; Microbiology ; history ; Molasses ; microbiology

A comparative study of batch and repeated batch process was carried out for astaxanthin fermentation of Phaffia rhodozyma to develop a more economical method for astaxanthin industrial production. In shaking flask fermentation, the change of biomass and astaxanthin production was studied to compare the five-day cycle with four-day cycle of repeated batch culture of P. rhodozyma. Astaxanthin production increased at first and then decreased subsequently in seven cycles, yet the yield of astaxanthin in the next six cycles remains higher than that of the first cycle. Comparing the average production of astaxanthin in the seven cycles, four-day cycle performed even better than five-day cycle. Subsequently, a repeated fed-batch process was used in a 5-1 bioreactor. The experimental data showed that biomass and astaxanthin production of the second batch could reach the level of the first batch, no matter that the carbon source was glucose or hydrolysis sugar of starch. This result showed that this strain had good stability, and thus repeated batch and fed-batch process could be applied in astaxanthin fermentation for economical purpose.
Basidiomycota ; genetics ; metabolism ; Batch Cell Culture Techniques ; methods ; Bioreactors ; microbiology ; Fermentation ; Industrial Microbiology ; methods ; Xanthophylls ; biosynthesis

To study the enrichment regulation of anammox bacteria during the whole start-up process of anammox reaction, two reactors with addition of carries of Spherical Plastic (SP) and Bamboo Charcoal (BC) and one without carrier (CK) were used to start anammox reaction. Then FISH and q-PCR analyses for the growth of all anammox bacteria were conducted during the operational process. The results indicate that the number of anammox bacteria in all reactors increased with time during the whole start-up process, which was consistent with the removal rate of ammonium and nitrite. On day 123 of stable phase, the percent of anammox cells in the sludge of CK, SP and BC accounted for 23.3%, 32.6% and 43.7%, respectively. The number of anammox bacteria 16S rRNA gene copies was (25.64 +/- 2.76) x 10(7), (47.12 +/- 2.76) x 10(7) and (577.99 +/- 27.25) x 10(7) copies g(-1) VSS in the sludge of CK, SP and BC, respectively. Carrier addition could dramatically increase enrichment of anammox bacteria. BC addition significantly increased the anammox bacteria number in the UASB reactor which resulted in the acceleration of the anammox start-up process. In addition, the max specific growth rate and the minimum doubling time were 0.064 d(-1) and 10.8 d in BC reactor. The max specific growth rate of anammox bacteria in BC reactor was 1.78 times and 1.88 times greater than that in CK and SP reactor, respectively. Therefore, the FISH and q-PCR analyses were suitable for determining the enrichment regulation of anammox bacteria during the start-up time, while a bit of differences in results existed between the two analytical methods due to the difference in analysis targets.
Ammonia ; metabolism ; Bacteria ; growth & development ; metabolism ; Bioreactors ; Industrial Microbiology ; Nitrites ; metabolism ; Oxidation-Reduction ; Sewage ; microbiology

Cell growth profiles were evaluated in shake-flask culture to improve sclareol production by the engineered yeast strain Saccharomyces cerevisiae S7. Product formation was tightly coupled with cell growth. High cell density cultures were performed with different carbon sources using a dissolved oxygen level feedback-control strategy in a 3 L bioreactor. The titers of sclareol were 253 mg/L, 386 mg/L and 408 mg/L, respectively, when glucose, ethanol and glucose/ethanol mixture were used as the carbons sources. The maximal titer was 27-fold higher than that obtained under shake-flask culture conditions. The results suggested that the presence of ethanol was beneficial to sclareol production. These results provided useful information for optimization of yeast cell factory and efficient production of terpenoids.
Bioreactors ; Culture Media ; Diterpenes ; metabolism ; Ethanol ; Glucose ; Industrial Microbiology ; methods ; Oxygen ; Saccharomyces cerevisiae ; metabolism

To study the effect of preservation temperature on the characteristics of anaerobic ammonium oxidation (Anammox) granules and optimize the preservation temperature of Anammox granules, the Anammox granules were cultivated in an upflow anaerobic sludge bed reactor through adjusting the hydraulic retention times, and the inorganic carbon with KHCO3/NaHCO3 was alternately supplied. Subsequently, the enriched Anammox granules were preserved at -40, 4 and 35 °C, and ambient temperature of (27 ± 4) °C. NaHCO3 can be used as the inorganic carbon for the growth of anaerobic ammonium oxidizing bacterium (AnAOB). The best preservation temperature was 4 °C for maintaining Anammox biomass, Anammox activity, settleability, and the integrity of the Anammox granule and AnAOB cell structure. During the preservation period, the first-order exponential decay model can simulate the decay of Anammox biomass and activity, and the decay coefficients (bAN) of Anammox biomass and activity had positive correlation with the degree of AnAOB cell lysis. Meanwhile, the rate of Anammox biomass decay was larger than that of Anammox activity. The ratio of protein to polysaccharide in extracellular polymeric substances and heme c cannot effectively indicate the changes of Anammox granules settleability and activity, respectively, and the bioactivity has a negative association with the degree of AnAOB cell lysis.
Ammonia ; chemistry ; Anaerobiosis ; Bacteria, Anaerobic ; Biomass ; Bioreactors ; Carbon ; Models, Theoretical ; Oxidation-Reduction ; Sewage ; microbiology ; Temperature

The anaerobic granular sludge from an Internal Circulation (IC) reactor of a paper mill wastewater treatment plant were seeded in an Anammox upflow anaerobic sludge blanket reactor. After 185 days operation, the reactor was finally started up by increasing the influent ammonium and nitrite concentrations to 224 mg/L and 255 mg/L, respectively, with volumetric nitrogen removal rate increasing to 3.76 kg/(m3·d). The physicochemical characteristics of the cultivated Anammox granules were observed by scanning electron microscope, transmission electron microscope and Fourier Transform infrared spectroscopy (FTIR). Results suggested that during the start-up course, the granular sludge initially disintegrated and then re-aggregated. FTIR spectra results revealed that the Anammox granular sludge contained abundant functional groups, indicating that it may also possess good adsorption properties. The ecological structure of the granular sludge, analyzed by the metagenomic sequencing methods, suggested that the relative abundance of the dominant bacterial community in the seeding sludge, i.e., Proteobacteria, Firmicutes, Bacteroidetes, significantly reduced, while Planctomycetes which contains anaerobic ammonium oxidation bacteria remarkably increased from 1.59% to 23.24% in the Anammox granules.
Ammonia ; chemistry ; Bacteria ; Bioreactors ; Nitrogen ; chemistry ; Sewage ; microbiology ; Waste Disposal, Fluid ; methods ; Waste Water ; chemistry