Fermentation strategies for production of pharmaceutical terpenoids in engineered yeast

Terpenoids, also known as isoprenoids, are a broad and diverse class of plant natural products with significant industrial and pharmaceutical importance. Many of these natural products have antitumor, anti-inflammatory, antibacterial, antiviral, and antimalarial effects, support transdermal absorption, prevent and treat cardiovascular diseases, and have hypoglycemic activities. Production of these compounds are generally carried out through extraction from their natural sources or chemical synthesis. However, these processes are generally unsustainable, produce low yield, and result in wasting of substantial resources, most of them limited. Microbial production of terpenoids provides a sustainable and environment-friendly alternative. In recent years, the yeast Saccharomyces cerevisiae has become a suitable cell factory for industrial terpenoid biosynthesis due to developments in omics studies (genomics, transcriptomics, metabolomics, proteomics), and mathematical modeling. Besides that, fermentation development has a significant importance on achieving high titer, yield, and productivity (TYP) of these compounds. Up to now, there have been many studies and reviews reporting metabolic strategies for terpene biosynthesis. However, fermentation strategies have not been yet comprehensively discussed in the literature. This review summarizes recent studies of recombinant production of pharmaceutically important terpenoids by engineered yeast, S. cerevisiae, with special focus on fermentation strategies to increase TYP in order to meet industrial demands to feed the pharmaceutical market. Factors affecting recombinant terpenoids production are reviewed (strain design and fermentation parameters) and types of fermentation process (batch, fed-batch, and continuous) are discussed.info:eu-repo/semantics/publishedVersio

Valorisation of waste bread for the production of yeast biomass by yarrowia lipolytica bioreactor fermentation

The increase in the wastage of bread, representing 12.5 million tons per year, causes ecological problems, such as the production of methane and CO2, when that waste bread (WB) is improperly managed. To reduce this ecological footprint, a more sustainable system of WB management must be set up. Based on its chemical composition, WB has a high potential to be used as feedstock for microbial growth and conversion into value-added bio products. The microbial valorisation of WB is a novel biotechnological approach to upgrading a waste into a renewable feedstock for bio-based industry, thus favouring the circular economy concept. Based on this, the aim of this study was to test WB as a feedstock for biomass production by Yarrowia lipolytica, which can be considered as a promising supplement for animal and human dietary products. The enzymatic hydrolysis of WB was primarily optimized for large-scale production in a bioreactor. The biomass production of Y. lipolytica strain K57 on WB hydrolysate-based media in batch bioreactor culture was then investigated. As a result, a very high starch to glucose conversion yield of 97% was obtained throughout optimised hydrolysis. At the end of 47 h of batch culture, a biomass higher than 62 g/L, specific growth rate of 0.37 h−1 and biomass yield of 0.45 g/g were achieved from a WB hydrolysate. Therefore, this study demonstrates that WB hydrolysate has a promising potential to be used as a feedstock for biomass production by Y. lipolytica strain K57 for food and animal diet applications.info:eu-repo/semantics/publishedVersio

Peptide extract from spent yeast improves resistance of Saccharomyces cerevisiae to oxidative stress

Yeast cells face various stress factors during industrial fermentations, since they are exposed to harsh environmental conditions, which may impair biomolecules productivity and yield. In this work, the use of an antioxidant peptide extract obtained from industrial spent yeast was explored as supplement for Saccharomyces cerevisiae fermentation to prevent a common bottleneck: oxidative stress. For that, a recombinant yeast strain, producer of β-farnesene, was firstly incubated with 0.5 and 0.7 g/L peptide extract, in the presence and absence of hydrogen peroxide (an oxidative stress inducer), for 1–5 h, and then assayed for intracellular reactive oxygen species, and growth ability in agar spot assays. Results showed that under 2 mM H2O2, the peptide extract could improve cells growth and reduce reactive oxygen species production. Therefore, this antioxidant effect was further evaluated in shake-flasks and 2-L bioreactor batch fermentations. Peptide extract (0.7 g/L) was able to increase yeast resistance to the oxidative stress promoted by 2 mM H2O2, by reducing reactive oxygen species levels between 1.2- and 1.7-fold in bioreactor and between 1.2- and 3-fold in shake-flask fermentations. Moreover, improvements on yeast cell density of up to 1.5-fold and 2-fold, and on biomolecule concentration of up to 1.6-fold and 2.8-fold, in bioreactor and shake-flasks, respectively, were obtained. Thus, culture medium supplementation with antioxidant peptide extracted from industrial spent yeast is a promising strategy to improve fermentation performance while valuing biomass waste. This valorization can promote a sustainable and eco-friendly solution for the biotechnology industry by the implementation of a circular economy model.info:eu-repo/semantics/publishedVersio

Examination of optimum test conditions for a 3-point bending and cutting test to evaluate sound emission of wafer during deformation

The purpose of this study was to investigate optimum test conditions of acoustical-mechanical measurement of wafer analysed by Acoustic Envelope Detector attached to the Texture Analyser. Force-displacement and acoustic signals were simultaneously recorded applying two different methods (3-point bending and cutting test). In order to study acoustical-mechanical behaviour of wafers, the parameters “maximum sound pressure”, “total count peaks” and “mean sound value” were used and optimal test conditions of microphone position and test speed were examined. With a microphone position of 45° angle and 1 cm distance and at a low test speed of 0.5 mm/s wafers of different quality could be distinguished best. The angle of microphone did not have significant effect on acoustic results and the number of peaks of the force and acoustic signal decreased with increasing distance and test speed

Production of oils and fats by oleaginous microorganisms with an emphasis given to the potential of the nonconventional yeast Yarrowia lipolytica

PubMedID: 29764205Recently, there has been a great upsurge of interest in studies related to several aspects of microbial lipid production, which is one of the top topics in relevant research fields due to the high demand of these fatty materials in food, medical, oleochemical and biofuel industries. Lipid accumulation by the so-called “oleaginous microorganisms” can generate more than 20% w/w of oil in dry biomass and is governed by a plethora of parameters, such as medium pH, incubation temperature, nutrient limitation and C/N (carbon/nitrogen) ratio, which drastically affect the lipid production bioprocess. Until now, considerable work has been undertaken to find the cheapest substrate to enable lipid fermentation by oleaginous microorganisms. This review principally details information regarding microbial lipids, suitable production conditions and focuses attention on using the yeast Yarrowia lipolytica to achieve these objectives. Lipid production by this yeast is discussed and the necessary conditions and suitable substrates are reviewed. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group

“In principio era il diritto all’acqua”: la dimensione morale come motore dell’azione collettiva per l’acqua pubblica

Il contributo di Davide Mazzoni e Elvira Cicognani, a partire da un approccio di psicologia sociale, riflette sulla dimensione morale della protesta, illustrando uno dei motori del successo della campagna referendaria. Dopo aver introdotto brevemente la letteratura sui processi di azione collettiva, il capitolo approfondisce le ragioni dell’identificazione con il movimento e della partecipazione alla campagna referendaria da parte di molti cittadini. In particolare, il saggio evidenzia che tale partecipazione è stata favorita dalla vasta percezione dell’acqua come un diritto, che le norme oggetto del referendum stavano in qualche modo violando. Il capitolo si basa sui risultati di un pool di studi recenti, condotti attraverso diverse metodologie (sia di tipo qualitativo, come le interviste, che quantitativo, come le inchieste campionarie)

Lipids by yarrowia lipolytica strains cultivated on glucose in batch cultures

Oleaginous microorganisms, such as Yarrowia lipolytica, accumulate lipids that can have interesting applications in food biotechnology or the synthesis of biodiesel. Y. lipolytica yeast can have many advantages such as wide substrate range usage and robustness to extreme conditions, while under several culture conditions it can produce high lipid productivity. Based on this assumption, in this study, 12 different Yarrowia lipolytica strains were used to investigate microbial lipid production using a glucose-based medium under nitrogen-limited conditions in shake-flask cultivations. Twelve wild-type or mutant strains of Yarrowia lipolytica which were newly isolated or belonged to official culture collections were tested, and moderate lipid quantities (up to 1.30 g/L) were produced; in many instances, nitrogen limitation led to citric acid production in the medium. Lipids were mainly composed of C16 and C18 fatty acids. Most of the fatty acids of the microbial lipid were unsaturated and corresponded mainly to oleic, palmitic and linoleic acids. Linolenic acid (C18:3) was produced in significant quantities (between 10% and 20%, wt/wt of dry cell weight (DCW)) by strains H917 and Po1dL. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.FDK-2014-315

Citric acid production by yarrowia lipolytica

peer reviewedRecently, with an increasing annual demand of more than two million tons, citric acid (CA) has become the main additive and functional component in the food, pharmaceutical, and chemical industries. This rising demand has induced research to search for alternative and cheap ways to fulfil CA requirements in industry. Lately, Yarrowia lipolytica has been considered as a promising microorganism in the production of CA since it has many advantages over moulds: mainly high productivity, easier cultivation (convenient for continuous process), and the capability to use a wide range of agricultural or industrial by-products and wastes as cheap carbon sources. CA production by this yeast depends on certain factors such as medium composition (type and concentrations of carbon, nitrogen, and trace elements) and the type of strain used (wild, mutant, or genetically engineered), as well as cultivation conditions (pH, temperature, dissolved oxygen, etc.). This review principally details recent studies concerning CA production by Y. lipolytica with an emphasis on techniques to increase productivity and yield to meet the expanding demand for this organic acid. Suitable substrates and production factors for high and cost-efficient CA production are discussed. Downstream processes and production systems are also reviewed. © Springer Nature Switzerland AG 2019

Phenolic compounds modulation in β-farnesene fed-batch fermentation using sugarcane syrup as feedstock

Sugarcane syrup is the feedstock used in the industrial production of β-farnesene through Saccharomyces cerevisiae fermentation. However, it contains phenolic compounds, which may interfere with yeast performance. The aim of this work was to modulate the transfer of phenolic compounds from sugarcane syrup to the broth, throughout 13 days of β-farnesene fed-batch fermentation in 2-L bioreactors. This was accomplished by applying two mathematical calculations: a mass balance and the Weibull kinetic model. The concentrations of most phenolic compounds increased until day 3 of fermentation and then remained constant until the end of the process. However, quantities of hydroxybenzaldehyde, protocatechuic, caffeic, ferulic and p-coumaric acids, decreased after day 2. The Weibull model exhibited better fit to the data, with an R2 of 0.85 or higher. This work provides for the first time a model describing phenolic accumulation in β-farnesene fermentation, which can be a valuable tool to apply in similar processes.info:eu-repo/semantics/acceptedVersio