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To determine the effects of microbial proteins on Qingzhuan tea sensory quality during tea pile fermentation, tea leaf metabolomic and microorganism proteomic analyses were performed. In total, 1835 differential metabolites and 443 differentially expressed proteins of the microorganisms were identified. Correlation analysis between metabolomics and proteomics data revealed that the levels of microbial proteins EG II and CBH I cellulase may play important roles in cell wall construction and permeability, which were crucial for the interaction between tea leaves and microorganisms. Microbial proteins heat shock proteins (HSP), alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and CuAO related to detoxification and stress responses showed a positive correlation with tea theanine, glutamine, γ-aminobutyric acid, glutamic acid, catechin, (-)-gallocatechin gallate, and (-)-catechin gallate, suggesting their effects on tea characteristic compound accumulation, thus affecting Qingzhuan tea sensory quality.

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Soft sensors based on deep learning regression models are promising approaches to predict real-time fermentation process quality measurements. However, experimental datasets are generally sparse and may contain outliers or corrupted data. This leads to insufficient model prediction performance. Therefore, datasets with a fully distributed solution space are required that enable effective exploration during model training. In this study, the robustness and predictive capability of the underlying model of a soft sensor was improved by generating synthetic datasets for training. The monitoring of intensified ethanol fermentation is used as a case study. Variational autoencoders were employed to create synthetic datasets, which were then combined with original datasets (experimental) to train neural network regression models. These models were tested on original versus augmented datasets to assess prediction improvements. Using the augmented datasets, the soft sensor predictive capability improved by 34%, and variability was reduced by 82%, based on R2 scores. The proposed method offers significant time and cost savings for dataset generation for the deep learning modeling of ethanol fermentation and can be easily adapted to other fermentation processes. This work contributes to the advancement of soft sensor technology, providing practical solutions for enhancing reliability and robustness in large-scale production.

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In Bacillus fermentation processes, severe foam formation may occur in aerated bioreactor systems caused by surface-active lipopeptides. Although they represent interesting compounds for industrial biotechnology, their property of foaming excessively during aeration may pose challenges for bioproduction. One option to turn this obstacle into an advantage is to apply foam fractionation and thus realize in situ product removal as an initial downstream step. Here we present and evaluate a method for integrated foam fractionation. A special feature of this setup is the external foam column that operates separately in terms of, e.g., aeration rates from the bioreactor system and allows recycling of cells and media. This provides additional control points in contrast to an internal foam column or a foam trap. To demonstrate the applicability of this method, the foam column was exemplarily operated during an aerated batch process using the surfactin-producing Bacillus subtilis strain JABs24. It was also investigated how the presence of lipopeptides and bacterial cells affected functionality. As expected, the major foam formation resulted in fermentation difficulties during aerated processes, partially resulting in reactor overflow. However, an overall robust performance of the foam fractionation could be demonstrated. A maximum surfactin concentration of 7.7 g/L in the foamate and enrichments of up to 4 were achieved. It was further observed that high lipopeptide enrichments were associated with low sampling flow rates of the foamate. This relation could be influenced by changing the operating parameters of the foam column. With the methodology presented here, an enrichment of biosurfactants with simultaneous retention of the production cells was possible. Since both process aeration and foam fractionation can be individually controlled and designed, this method offers the prospect of being transferred beyond aerated batch processes.

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Hyaluronic acid (HA) is a glycosaminoglycan widely distributed in the human body, especially in body fluids and the extracellular matrix of tissues. It plays a crucial role not only in maintaining tissue hydration but also in cellular processes such as proliferation, differentiation, and the inflammatory response. HA has demonstrated its efficacy as a powerful bioactive molecule not only for skin antiaging but also in atherosclerosis, cancer, and other pathological conditions. Due to its biocompatibility, biodegradability, non-toxicity, and non-immunogenicity, several HA-based biomedical products have been developed. There is an increasing focus on optimizing HA production processes to achieve high-quality, efficient, and cost-effective products. This review discusses HA's structure, properties, and production through microbial fermentation. Furthermore, it highlights the bioactive applications of HA in emerging sectors of biomedicine.

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Vinegar is one of the most widely used acidic condiments. Recently, rapid advances have been made in the area of vinegar research. Different types of traditional vinegar are available around the globe and have many applications. Vinegar can be made either naturally, through alcoholic and then acetic acid fermentation, or artificially, in laboratories. Vinegar is the product of acetic acid fermentation of dilute alcoholic solutions, manufactured by a two-step process. The first step is the production of ethanol from a carbohydrate source such as glucose, which is carried out by yeasts. The second step is the oxidation of ethanol to acetic acid, which is carried out by acetic acid bacteria. Acetic acid bacteria are not only producers of certain foods and drinks, such as vinegar, but they can also spoil other products such as wine, beer, soft drinks, and fruits. Various renewable substrates are used for the efficient biological production of acetic acid, including agro and food, dairy, and kitchen wastes. Numerous reports on the health advantages associated with vinegar ingredients have been presented. Fresh sugarcane juice was fermented with wine yeast and LB acetate bacteria to develop a high-quality original sugarcane vinegar beverage. To facilitate the current study, the bibliometric analysis method was adopted to visualize the knowledge map of vinegar research based on literature data. The present review article will help scientists discern the dynamic era of vinegar research and highlight areas for future research.

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This article purposed to discuss the connection between microbiota and characteristic flavor of different fish sauces (Natural fermentation (WQ), koji outdoor fermentation (YQ), heat preservation with enzyme (BWE), and heat preservation with koji (BWQ)) at the early (3 months) and late stage (7 months). A total of 117 flavor compounds were determined according to SPME-GC-MS analysis. O2PLS-DA and VIP values were used to reveal 15 and 28 flavor markers of different fish sauces at 3 and 7 M of fermentation. Further, the possible flavor formation pathways were analyzed using metagenomic sequencing, and the key microbes associated with flavor formation were identified at the genetic level. The top 10 genera related to flavor generation, such as Lactobacillus, Staphylococcus, Enterobacter, etc., appeared to play a prominent part in the flavor formation of fish sauce. The difference was that only BWQ and BWE groups could produce ethyl-alcohol through amino acid metabolism, while YQ, BWE and BWQ groups could generate phenylacetaldehyde through the transformation of Phe by α-ketoacid decarboxylase and aromatic amino acid transferase. Our research contributes to clarifying the various metabolic roles of microorganisms in the flavor generation of fish sauce.

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Currently, researchers have focused on electrokinetic (EK) bioremediation due to its potential to remove a wide-range of pollutants. Further, to improve their performance, synthetic surfactants are employed as effective additives because of their excellent solubility and mobility. Synthetic surfactants have an excessive position in industries since they are well-established, cheap, and easily available. Nevertheless, these surfactants have adverse environmental effects and could be detrimental to aquatic and terrestrial life. Owing to social and environmental awareness, there is a rising demand for bio-based surfactants in the global market, from environmental sustainability to public health, because of their excellent surface and interfacial activity, higher and stable emulsifying property, biodegradability, non- or low toxicity, better selectivity and specificity at extreme environmental conditions. Unfortunately, challenges to biosurfactants, like expensive raw materials, low yields, and purification processes, hinder their applicability to large-scale. To date, extensive research has already been conducted for production scale-up using multidisciplinary approaches. However, it is still essential to research and develop high-yielding bacteria for bioproduction through traditional and biotechnological advances to reduce production costs. Herein, this review evaluates the recent progress made on microbial-surfactants for bioproduction scale-up and provides detailed information on traditional and advanced genetic engineering approaches for cost-effective bioproduction. Furthermore, this study emphasized the role of electrokinetic (EK) bioremediation and discussed the application of BioS-mediated EK for various pollutants remediation.

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This study addresses the design of advanced control schemes implemented for a continuous fermentation process used to produce ethanol. Due to the inaccuracy of the models that express this complex process, a feasible controller is required to maximize the production of ethanol and to minimize its environmental impact, despite the existence of some significant uncertainties. Therefore, novel estimation and control schemes are designed and tested. These schemes are adaptive control laws including nonlinear estimation algorithms: a sliding mode observer to estimate the unknown influent concentration, but also state observers and parameter estimators used to estimate the unknown states and kinetics. Since the temperature is an important factor for an efficient operation of the process, an algorithm for temperature control in the bioreactor is also developed. To verify the control algorithms effectiveness, several tests performed via numerical simulations under realistic conditions are presented.

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Gradients in industrial bioreactors have attracted substantial research attention since exposure to fluctuating environmental conditions has been shown to lead to changes in the metabolome, transcriptome as well as population heterogeneity in industrially relevant microorganisms. Such changes have also been found to impact key process parameters like the yield on substrate and the productivity. Hence, understanding gradients is important from both the academic and industrial perspectives. In this review the causes of gradients are outlined, along with their impact on microbial physiology. Quantifying the impact of gradients requires a detailed understanding of both fluid flow inside industrial equipment and microbial physiology. This review critically examines approaches used to investigate gradients including large-scale experimental work, computational methods and scale-down approaches. Avenues for future work have been highlighted, particularly the need for further coordinated development of both in silico and experimental tools which can be used to further the current understanding of gradients in industrial equipment.

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Accurate and real-time quality prediction to realize the optimal process control at a competitive price is an important issue in Industrial 4.0. This paper shows a successful engineering application of how smart soft sensors can be combined with machine learning technique to significantly save human resources and improve performance under complex industrial conditions. Ensemble learning based soft sensors succeed in capturing complex nonlinearities, frequent dynamic changes, as well as time-varying characteristics in industrial processes. However, local model regions under traditional ensemble modelling methods are highly dependent on labeled data samples and, hence, their prediction accuracy might get affected when labeled samples are limited. A novel active learning (AL) framework upon the ensemble Gaussian process regression (GPR) model is proposed for smart soft sensor design in order to overcome this drawback. Firstly, to iteratively select the most informative unlabeled samples for labeling with hierarchical sampling based AL strategy, to then apply Gaussian mixture model (GMM) technique to autonomously identify operation phases, to further construct local GPR models without human involvement, and finally to integrate the base predictors by applying the Bayesian fusion strategy. Comparative studies for the penicillin fermentation process demonstrate the reliability and superiority of the recommended smart soft sensing. The cost of human annotation can be dramatically reduced by at least half while the prediction performance simultaneously keeps high.

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Statins are drugs used for people with abnormal lipid levels (hyperlipidemia) and are among the best-selling medications in the United States. Thus, the aspects related to the production of these drugs are of extreme importance for the pharmaceutical industry. Herein, we provide a non-exhaustive review of fungal species used to produce statin and highlighted the major factors affecting the efficacy of this process. The current biotechnological approaches and the advances of a metabolic engineer to improve statins production are also emphasized. The biotechnological production of the main statins (lovastatin, pravastatin and simvastatin) uses different species of filamentous fungi, for example Aspergillus terreus. The statins production is influenced by different types of nutrients available in the medium such as the carbon and nitrogen sources, and several researches have focused their efforts to find the optimal cultivation conditions. Enzymes belonging to Lov class, play essential roles in statin production and have been targeted to genetic manipulations in order to improve the efficiency for Lovastatin and Simvastatin production. For instance, Escherichia coli strains expressing the LovD have been successfully used for lovastatin production. Other examples include the use of iRNA targeting LovF of A. terreus. Therefore, fungi are important allies in the fight against hyperlipidemias. Although many studies have been conducted, investigations on bioprocess optimization (using both native or genetic- modified strains) still necessary.

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Cacao fermentation induces biochemical changes in the beans that lead to different cacao grades such as slaty (unfermented), violet (under fermented) and brown (fully fermented) beans. This grade heterogeneity in a sample set can impact the quality of the end-products. In the present study, amino acids and polyphenol contents of slaty, violet and brown beans were evaluated. Free amino acids were derivatized from o-phthalaldehyde and detected with a fluorescence spectrophotometer coupled with a reverse phase HPLC system. Polyphenols were analysed at 280 nm by HPLC using a Photodiode Array Detector. Amino acids content in the violet beans were significantly higher (11,165 ± 4281 mg kg-1 fat free dry material, ffdm) than that of the slaty beans (4304.5 ± 1927.6 mg kg-1 ffdm), meanwhile there was no significant difference between violet and brown beans. Epicatechin, catechin, cyanidin-3-arabinoside and cyanidin-3-galactoside contents were significantly lower in violet and brown beans when compared to slaty beans. Our results have shown that a mixture of violet and brown beans is suitable to obtain polyphenols and amino acids in the development of cacao products.

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Food waste is the single-largest component of the waste stream, in order to protect and safeguard the public health, useful and innovative recycling methods are investigated. The conversion of food wastes in value-added products is becoming a more economically viable and interesting practice. Food waste, collected in the distribution sector and citrus industries, was characterised for its potential as a raw material to use in fermentation processes. In this study, the production of single-cell protein (SCP) using food waste as a substrate was investigated. The purpose of this study has been to produce SCP from mixtures of food waste using Saccharomyces cerevisiae. The main fermentation test was carried out using a 25 l bioreactor. The utilisation of food waste can allow us to not only to reduce environmental pollution, but also to obtain value-added products such as protein supply for animal feed.

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Waste deriving from food and agro-industries is a growing problem in our modern society. In order to reduce food waste and its associated impacts over the environment and public health, innovative strategies for the conversion of food wastes in added value products are studied. Whey is one of the prominent waste deriving from Sicilian diary industry. The growth and the carotenoid biosynthesis of the yeast Xanthophyllomyces dendrorhous by its cultivation in pre-treated whey were studied. The study showed the possibility of increasing the astaxanthin productivity from X. dendrorhous in a batch fermentative process under continuous illumination. Our work is focused on the importance of carotenogenesis by X. dendrorhous on whey for the economic and ecological aspect. The results obtained in the study provide useful information about the possible use of this waste material for carotenogenesis from X. dendrorhous.

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For any fermentation process, the production cost depends on several factors, such as the genetics of the microorganism, the process condition, and the culture medium composition. In this work, a guideline for the design of cost-efficient culture media using a sequential approach based on response surface methodology is described. The procedure was applied to analyze and optimize a culture medium of registered trademark and a base culture medium obtained as a result of the screening analysis from different culture media used to grow the same strain according to the literature. During the experiments, the procedure quantitatively identified an appropriate array of micronutrients to obtain a significant yield and find a minimum number of culture medium ingredients without limiting the process efficiency. The resultant culture medium showed an efficiency that compares favorably with the registered trademark medium at a 95% lower cost as well as reduced the number of ingredients in the base culture medium by 60% without limiting the process efficiency. These results demonstrated that, aside from satisfying the qualitative requirements, an optimum quantity of each constituent is needed to obtain a cost-effective culture medium. Study process variables for optimized culture medium and scaling-up production for the optimal values are desirable.

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Anthocyanins are the major polyphenolic compounds in strawberry fruit responsible for its color. Due to their sensitivity, they are affected by food processing techniques such as fermentation that alters both their chemical composition and organoleptic properties. This work aims to evaluate the impact of different fermentation processes on individual anthocyanins compounds in strawberry wine and vinegar by UHPLC-MS/MS Q Exactive analysis. Nineteen, 18, and 14 anthocyanin compounds were identified in the strawberry initial substrate, strawberry wine, and strawberry vinegar, respectively. Four and 8 anthocyanin compounds were tentatively identified with high accuracy for the 1st time to be present in the beverages obtained by alcoholic fermentation and acetic fermentation of strawberry, respectively. Both, the total and the individual anthocyanin concentrations were decreased by both fermentation processes, affecting the alcoholic fermentation to a lesser extent (19%) than the acetic fermentation (91%). Indeed, several changes in color parameters have been assessed. The color of the wine and the vinegar made from strawberry changed during the fermentation process, varying from red to orange color, this fact is directly correlated with the decrease of anthocyanins compounds.

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This review highlights the importance of research for development of biofertilizer and biocontrol products based on the use of glycerol for further process scale-up to industrial microbiology. Glycerol can be used successfully in all stages of production of plant beneficial microorganisms. It serves as an excellent substrate in both submerged and solid-state fermentation processes with free and immobilized microbial cells. Glycerol is also one of the most attractive formulation agents that ensures high cell density and viability including in harsh environmental conditions. Future research is discussed to make this inexpensive material a base for industrial production of plant beneficial microorganisms.

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Clavulanic acid (CA) is an important secondary metabolite commercially produced by cultivation of Streptomyces clavuligerus (Sc). It is a potent inhibitor of bacterial ß-lactamases. In this work, a specific and improved high performance liquid chromatography (HPLC) method, using a C-18 reversed phase column, diode array detector and gradient elution for CA quantification in fermentation broths of Sc, was developed and successfully validated. Samples were imidazole-derivatized for the purpose of creating a stable chromophore (clavulanate-imidazole). The calibration curve was linear over a typical range of CA concentration between 0.2 and 400mg/L. The detection and quantification limits were 0.01 and 0.02mg/L, respectively. The precision of the method was evaluated for CA spiked into production media and a recovery of 103.8%, on average, was obtained. The clavulanate-imidazole complex was not stable when the samples were not cooled during the analysis. The recovery rate was 39.3% on average. This assay was successfully tested for CA quantification in samples from Sc fermentation, using both, a chemically defined and a complex medium.

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In aerobic metabolism, reactive oxygen species (ROS) are formed during the fermentation that can cause oxidative stress in microorganisms. Microbial cells possess both enzymatic and non-enzymatic defensive systems that may protect cells from oxidative damage. The antioxidant enzymes superoxide dismutase and catalase are the two key defensive enzymes to oxidative stress. The factors that induce oxidative stress in microorganisms include butylated hydroxytoluene (BHT), hydrogen peroxide, metal ions, dissolved oxygen tension, elevated temperature, menadione, junglone, paraquat, liquid paraffin, introduction to bioreactors of shake flask inocula and synthetic medium sterilized at initial pH 11.0. Carotenes are highly unsaturated isoprene derivatives. They are used as antioxidants and as coloring agents for food products. In fungi, carotenes are derived via the mevalonate biosynthesis pathway. The key genes in carotene biosynthesis are hmgR, ipi, isoA, carG, carRA and carB. Among microorganisms, Βlakeslea trispora is the main microorganism used for the production of carotenes on the industrial scale. Currently, the synthetic medium is considered the superior substrate for the production of carotenes in a pilot plant scale. The fermentation systems used for the production of carotenes include shake flasks, stirred tank fermentor, bubble column reactor and flat panel photobioreactor. This review summarizes the oxidative stresses in microorganisms and it is focused on the current status of carotene production by B. trispora including oxidative stress induced by BHT, enhanced dissolved oxygen levels, iron ions, liquid paraffin and synthetic medium sterilized at an initial pH 11.0. The oxidative stress induced by the above factors increases significantly the production of carotenes. However, to further reduce the cost of carotene production, new biotechnological methods with higher productivity still need to be explored.

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