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

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

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

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

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

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

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

The yield of S-adenosyl-L-methionine (SAM) on high-cell-density fermentation by saccharomyces cerevisiae is mostly affected by the feeding strategy of pre-L-methionine. The mutant strain SAM0801 that could accumulate more SAM was used in this study. Six high-cell-density fermentation experiments in 5 L fermentor were investigated to get the optimal feeding time and amount of L-methionine. The results showed that when 40 g L-methionine was added in the fermentor after 30 h fermentation, a dry cell weight of 100 g/L was achieved. Under this condition, after 58 h fermentation, both the dry cell weight and the yield of SAM reached the maximum, 168 g/L and 14.48 g/L respectively.
Bioreactors ; microbiology ; Fermentation ; Methionine ; analysis ; metabolism ; Mutation ; S-Adenosylmethionine ; biosynthesis ; Saccharomyces cerevisiae ; genetics ; growth & development ; metabolism

Early-warning of compartmentalized anaerobic reactor (CAR) was investigated in lab-scale. The performance stability of CAR at high loading rate was worse than that at common loading rate. At high loading rate, the fluctuation of effluent chemical oxygen demand (COD) concentration and volatile fatty acids (VFA) concentration was larger than that of influent COD concentration. The average relative standard deviation of effluent COD concentration and VFA concentration was 32.95% and 40.46% respectively, while that of influent COD concentration was 8.08%. The saturation of volumetric loading rate (S(VLR)) and VFA (S(VFA)) could be used to alarm the performance of anaerobic reactors. The working performance was good when the CAR was operated at normal organic loading rate (OLR), in which S(VLR) and S(VFA) were below 0.89 and 0.40 respectively. The fluctuation of performance became larger when the CAR was operated at OLR near saturation, in which S(VLR) and S(VFA) were close to 1. The performance of CAR was deteriorated when the S(VLR) and S(VFA) were more than 1.
Anaerobiosis ; Biological Oxygen Demand Analysis ; Bioreactors ; microbiology ; Fatty Acids, Volatile ; analysis ; Sewage ; Waste Disposal, Fluid ; methods

A fermentation system composed of four airlift suspended-bed bioreactors in series and with a total working volume of 4800 mL was established. Continuous ethanol fermentation using self-flocculating yeast SPSC01, a fusant from Saccharomyces cerevisiae and Schizosaccharomyces pombe, and two-stage enzymatic hydrolyte of dry milling corn powder, was continuously run for 120 days. All of the backset distillage collected after distilling the final beer was used to mix the corn powder and no any other wastes except the solid residue of corn powder was discharged from the fermentation system, which guaranteed the distillage to be recycled at its maximum. The experimental results revealed that both ethanol and residual sugar in the final beer could be maintained relatively stable with their average levels of 93.6 and 7.9 g/L, respectively when the fermentation system was operated at the dilution rate of 0.05 h(-1). Parameter oscillations reported previously were also observed for the first and second bioreactors, but were effectively attenuated thereafter, which indicated that high yeast cell concentrations resulted from the self-immobilization of this special self-flocculating strain contributed to damp these oscillations. The monitoring of residual nitrogen and phosphor indicated that the accumulations of these nutritional elements occurred and the amount of these inorganic salts supplemented in the substrate should be decreased properly.
Bioreactors ; microbiology ; Ethanol ; metabolism ; Fermentation ; Flocculation ; Immobilization ; Saccharomyces cerevisiae ; metabolism ; Schizosaccharomyces ; metabolism ; Zea mays ; metabolism