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

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

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 internal-loop granular sludge bed nitrifying reactor is a new type of aerobic nitrifying equipment and has taken on a good potential for nitrification. The critical aerating flux for liquid loop and critical aerating flux for fluidization of granular sludge are two important parameters for its operation. The relationship between liquid superficial velocity in riser (U1r) and aerating flux(Ugr) was studied, the model parameters were measured by experiment, and the relational expression was established. According to the model, the critical aerating flux for liquid loop and the critical aerating flux for fluidization of granular sludge were calculated as 1.017cm/min and 2.662cm/min, respectively. The experimental data from reactor operation showed that the two calculated critical aerating fluxes near the practical values. So they could be used to direct the design and operating optimization for the internal-loop granular sludge bed nitrifying reactor.
Bacteria, Aerobic ; metabolism ; Bioreactors ; Nitrites ; metabolism ; Sewage ; chemistry ; microbiology ; Waste Disposal, Fluid ; methods

Gluconobacter oxydans is known to oxidize glucose to gluconic acid (GA), and subsequently, to 2-keto-gluconic acid (2KGA) and 5-keto-gluconic acid (5KGA), while 5KGA can be converted to L-(+)-tartaric acid. In order to increase the production of 5KGA, Gluconobacter oxydans HGI-1 that converts GA to 5KGA exclusively was chosen in this study, and effects of carbon sources (lactose, maltose, sucrose, amylum and glucose) and nitrogen sources (yeast extract, fish meal, corn steep liquor, soybean meal and cotton-seed meal) on 5KGA production were investigated. Results of experiment in 500 mL shake-flask show that the highest yield of 5KGA (98.20 g/L) was obtained using 100 g/L glucose as carbon source. 5KGA reached 100.20 g/L, 109.10 g/L, 99.83 g/L with yeast extract, fish meal and corn steep liquor as nitrogen source respectively, among which the optimal nitrogen source was fish meal. The yield of 5KGA by corn steep liquor is slightly lower than that by yeast extract. For the economic reason, corn steep liquor was selected as nitrogen source and scaled up to 5 L stirred-tank fermentor, and the final concentration of 5KGA reached 93.80 g/L, with its maximum volumetric productivity of 3.48 g/(L x h) and average volumetric productivity of 1.56 g/(L x h). The result obtained in this study showed that carbon and nitrogen sourses for large-scale production of 5KGA by Gluconobacter oxydans HGI-1 were glucose and corn steep liquor, respectively, and the available glucose almost completely (85.93%) into 5KGA.
Bioreactors ; Carbon ; chemistry ; Culture Media ; chemistry ; Fermentation ; Gluconates ; metabolism ; Gluconobacter oxydans ; metabolism ; Industrial Microbiology ; Nitrogen ; chemistry

To evaluate the effectiveness of enzymatic assisted extraction (EAE) of lipid from the oleaginous yeast Rhodosporidium toruloides in the presence of beta-1,3-glucomannanase at a larger scale, we investigated the effects of enzymatic treatment and extraction conditions on lipid extraction yields at 10-L scale by using the broth of R. toruloides Y4 as the feed and ethyl acetate as the solvent. When it was treated for 0.5 h, the lipid extraction yield reached 71.1%, indicating that the enzymatic treatment process reached similar efficiency to that obtained at 10-mL scale. The inhibitory effect of emulsification was greatly reduced by repeated extraction. After extracted for three times, yields of lipid extraction, solvent recovery and total material recovery reached 92.9%, 87.0% and 94.2% respectively. As it can use the lipid production slurry with good extraction efficiency, EAE technology is promising for industrial production of microbial lipids.
Basidiomycota ; metabolism ; Biofuels ; Bioreactors ; Fermentation ; Industrial Microbiology ; Lipids ; biosynthesis ; isolation & purification ; beta-Mannosidase ; metabolism