A review of the state of sweeteners science: the natural versus artificial non-caloric sweeteners debate. Stevia rebaudiana and Siraitia grosvenorii into the spotlight.

The rapid increase in the worldwide prevalence of obesity and certain non-communicable diseases (NCDs), such as: cardiovascular diseases, cancers, chronic respiratory diseases, and diabetes, has been mainly attributed to an excess of sugar consumption. Although the potential benefits of the synergetic use of sweeteners have been known for many years, recent development based on synthesis strategies to produce sucrose-like taste profiles is emerging where biocatalyst approaches may be preferred to produce and supply specific sweetener compounds. From a nutritional standpoint, high-intensity sweeteners have fewer calories than sugars while providing a major sweet potency, placing them in the spotlight as valuable alternatives to sugar. Due to the modern world awareness and incidence of metabolic diseases, both food research and growing markets have focused on two generally regarded as safe (GRAS) groups of compounds: the sweet diterpenoid glycosides present on the leaves of Stevia rebaudiana and, more recently, on the cucurbitane triterpene glycosides present on the fruits of Siraitia grosvenorii. In spite of their flavor advantages, biological benefits, including: antidiabetic, anticancer, and cardiovascular properties, have been elucidated. The present bibliographical review dips into the state-of-the-art of sweeteners and their role in human health as sugar replacements, as well as the biotransformation methods for steviol gylcosides and mogrosides apropos of enzymatic technology to update and locate the discoveries to date in the scientific literature to help boost the continuity of research efforts of the ongoing sweeteners.

D-Allulose Reduces Hypertrophy and Endoplasmic Reticulum Stress Induced by Palmitic Acid in Murine 3T3-L1 Adipocytes.

Natural rare sugars are an alternative category of sweeteners with positive physiologic and metabolic effects both in in vitro and animal models. D-allulose is a D-fructose epimer that combines 70% sucrose sweetness with the advantage of an extremely low energy content. However, there are no data about the effect of D-allulose against adipose dysfunction; thus, it remains to be confirmed whether D-allulose is useful in the prevention and in treatment of adipose tissue alterations. With this aim, we evaluated D-allulose's preventive effects on lipid accumulation in 3T3-L1 murine adipocytes exposed to palmitic acid (PA), a trigger for hypertrophic adipocytes. D-allulose in place of glucose prevented adipocyte hypertrophy and the activation of adipogenic markers C/EBP-ß and PPARγ induced by high PA concentrations. Additionally, D-allulose pretreatment inhibited the NF-κB pathway and endoplasmic reticulum stress caused by PA, through activation of the Nrf2 pathway. Interestingly, these effects were also observed as D-allulose post PA treatment. Although our data need to be confirmed through in vivo models, our findings suggest that incorporating D-allulose as a glucose substitute in the diet might have a protective role in adipocyte function and support a unique mechanism of action in this sugar as a preventive or therapeutic compound against PA lipotoxicity through the modulation of pathways connected to lipid transport and metabolism.

Absorption and Metabolism of the Natural Sweeteners Erythritol and Xylitol in Humans: A Dose-Ranging Study.

The natural sweeteners erythritol and xylitol might be helpful to reduce sugar consumption and therefore prevent obesity and diabetes. The aim of the present study was to determine the absorption and metabolization into erythronate of different concentrations of erythritol and xylitol. Seventeen healthy lean participants received intragastric solutions of 10, 25, or 50 g erythritol or 7, 17, or 35 g xylitol on three study days in a randomized order. The study was double blinded with respect to the doses administered. We assessed plasma concentrations of erythritol, xylitol, and erythronate at fixed time intervals after administration with gas chromatography-mass spectrometry. We found: (i) a dose-dependent and saturable absorption of erythritol, (ii) a very low absorption of xylitol, (iii) a dose-dependent metabolization of erythritol into erythronate, and (iv) no metabolization of xylitol into erythronate. The implications of the metabolization of erythritol into erythronate for human health remain to be determined and more research in this area is needed.

Gastric emptying of solutions containing the natural sweetener erythritol and effects on gut hormone secretion in humans: A pilot dose-ranging study.

AIM: To determine whether a dose-dependent effect in the stimulation of gut hormone release (plasma cholecystokinin [CCK], active glucagon-like peptide-1 [aGLP-1] and peptide tyrosine tyrosine [PYY]) is found for the natural sweetener erythritol. MATERIALS AND METHODS: Twelve healthy, lean volunteers received solutions with 10, 25 or 50 g erythritol, or tap water enriched with 13 C-sodium acetate on four study days via a nasogastric tube in this randomized (active treatments), placebo-controlled, double-blind, cross-over trial. Blood samples and breath samples (13 C-sodium acetate method for measurement of gastric emptying [GE]) were taken at regular intervals, and sensations of appetite and gastrointestinal symptoms were rated. RESULTS: We found (a) a dose-dependent stimulation of CCK, aGLP-1 and PYY, and slowing of GE, (b) no effect on blood glucose, insulin, motilin, glucagon or glucose-dependent insulinotropic polypeptide, (c) no effect on blood lipids and uric acid, and (d) no abdominal pain, nausea or vomiting. CONCLUSIONS: Solutions with 10 and 50 g of erythritol stimulated gut hormone release. Emptying of erythritol-containing solutions from the stomach was slower compared with placebo. There was no effect on plasma glucose, insulin, glucagon, blood lipids or uric acid. All doses were well tolerated.

Effect of short-term intake of four sweeteners on feed intake, solution consumption and neurotransmitters release on mice.

This study focused on the effect of short-term intake of sweeteners on feed intake, solution consumption and neurotransmitters release on mice. The results showed that the free drinking of 10 mM sucralose solution, 100 mM maltose solution, 3 mM saccharin solution and 3 g/L stevioside solution for 32 days will not affect the normal development of the body weight and feed intake of the mice. The consumption of maltose solution was significantly higher than that of the other sweeteners. The leptin and insulin levels increased significantly after the short-term intake of these four sweeteners. The dopamine (DA) content in the whole brain of the mice increased significantly only in the maltose group. These results indicate that the short-term intake of the preferred concentrations of maltose, stevioside, sucralose and saccharin will not affect the body weight and feed intake of the mice. Mice prefer maltose solution to other sweeteners solutions. The 100 mM maltose solution and 3 mM saccharin solution could result in the oxidative stress on mice after 32 days' short-term intake. Compared with other sweeteners, only sugars that could be broken down into small molecules of glucose might have a positive effect on dopamine levels.

Fixative properties of honey solutions as a formaldehyde substitute in cardiac tissue preservation.

OBJECTIVES: To evaluate the properties of natural sweetener solutions in whole organ preservation and assess their influence on the dimension, weight and shape of cardiac tissue samples in stated time intervals, up to a one-year period of observation. BACKGROUND: Tissue fixation is essential for biological sample examination. Many negative toxic effects of formaldehyde-based fixatives have forced us to seek alternatives for formaldehyde based solutions. It has been demonstrated that natural sweeteners can preserve small tissue samples well and that these solutions can be used in histopathological processes. However, their ability to preserve whole human organs are unknown. METHODS: A total of 30 swine hearts were investigated. Three study groups (n = 10 in each case) were formed and classified on the type of fixative: (1) 10% formaldehyde phosphate-buffered solution (FPBS), (2) 10% alcohol-based honey solution (ABHS), (3) 10% water-based honey solution (WBHS). Samples were measured before fixation and in the following time points: 24 hours, 72 hours, 168 hours, 3 months, 6 months and 12 months. RESULTS: The WBHS failed to preserve heart samples and decomposition of tissues was observed one week after fixation. In half of the studied parameters, the ABHS had similar modifying tendencies as compared to FPBS. e overall condition of preserved tissue, weight, left ventricular wall thickness, right ventricular wall thickness and the diameter of the papillary muscle differed considerably. CONCLUSIONS: The ABHS may be used as an alternative fixative for macroscopic studies of cardiac tissue, whereas the WBHS is not suited for tissue preservation.

Metabolites of Siamenoside I and Their Distributions in Rats.

Siamenoside I is the sweetest mogroside that has several kinds of bioactivities, and it is also a constituent of Siraitiae Fructus, a fruit and herb in China. Hitherto the metabolism of siamenoside I in human or animals remains unclear. To reveal its metabolic pathways, a high-performance liquid chromatography-electrospray ionization-ion trap-time of flight-multistage mass spectrometry (HPLC-ESI-IT-TOF-MS(n)) method was used to profile and identify its metabolites in rats. Altogether, 86 new metabolites were identified or tentatively identified, and 23 of them were also new metabolites of mogrosides. In rats, siamenoside I was found to undergo deglycosylation, hydroxylation, dehydrogenation, deoxygenation, isomerization, and glycosylation reactions. Among them, deoxygenation, pentahydroxylation, and didehydrogenation were novel metabolic reactions of mogrosides. The distributions of siamenoside I and its 86 metabolites in rat organs were firstly reported, and they were mainly distributed to intestine, stomach, kidney, and brain. The most widely distributed metabolite was mogroside IIIE. In addition, eight metabolites were bioactive according to literature. These findings would help to understand the metabolism and effective forms of siamenoside I and other mogrosides in vivo.

Stevia rebaudiana Leaves: Effect of Drying Process Temperature on Bioactive Components, Antioxidant Capacity and Natural Sweeteners.

Stevia leaves are usually used in dried state and undergo the inevitable effect of drying process that changes the quality characteristics of the final product. The aim of this study was to assess temperature effect on Stevia leaves through analysis of relevant bioactive components, antioxidant capacity and content of natural sweeteners and minerals. The drying process was performed in a convective dryer at constant temperatures ranging from 30 to 80 °C. Vitamin C was determined in the leaves and as expected showed a decrease during drying proportional to temperature. Phenolics and flavonoids were also determined and were found to increase during drying below 50 °C. Antioxidant activity was determined by DPPH and ORAC assays, and the latter showed the highest value at 40 °C, with a better correlation with the phenolics and flavonoids content. The content of eight natural sweeteners found in Stevia leaves was also determined and an increase in the content of seven of the sweeteners, excluding steviol bioside, was found at drying temperature up to 50 °C. At temperatures between 60 and 80 °C the increase in sweeteners content was not significant. Stevia leaves proved to be an excellent source of antioxidants and natural sweeteners.

Extraction, physicochemical properties, bioactivities and application of natural sweeteners: A review.

Natural sweeteners generally refer to a sweet chemical component directly extracted from nature or obtained through appropriate modifications, mainly secondary metabolites of plants. Compared to the first-generation sweeteners represented by sucrose and the second-generation sweeteners represented by sodium cyclamate, natural sweeteners usually have high sweetness, low-calorie content, good solubility, high stability, and rarely toxic side effects. Historically, researchers mainly focus on the function of natural sweeteners as substitutes for sugars in the food industry. This paper reviews the bioactivities of several typical natural sweeteners, including anti-cancer, anti-inflammatory, antioxidant, anti-bacterial, and anti-hyperglycemic activities. In addition, we have summarized the extraction, physicochemical properties, and application of natural sweeteners. The article aimed to comprehensively collate vital information about natural sweeteners and review the potentiality of tapping bioactive compounds from natural products. Hopefully, this review provides insights into the further development of natural sweeteners as therapeutic agents and functional foods.

The substitute ENSO 16 has low impact on glucose metabolism in healthy humans: a randomized, double-blind, active-controlled, cross-over trial.

High sugar consumption is associated with cardiovascular diseases and diabetes. Current sugar substitutes may cause taste sensations and gastrointestinal symptoms. ENSO 16 is a combination of 16 different sugar substitutes and plant fibers and has been designed as a sugar alternative. The impact on plasma glucose metabolism as well as on gastrointestinal tolerance has not been investigated yet. 17 healthy participants were enrolled in this randomized, double-blind trial. Participants received a single oral dose of 30 g glucose or 30 g ENSO 16 and crossed over to the alternate treatment after a 7 day wash out period. The study endpoint was the effect on plasma glucose, insulin, C-peptide concentrations and gastrointestinal disorders. A questionnaire regarding gastrointestinal symptoms was used for individual subjective scoring. The mean baseline adjusted plasma glucose AUC0-180 min was significantly greater after glucose administration compared to ENSO 16 (n = 15, p = 0.0128, paired t-test). Maximum plasma glucose elevation over baseline was 117 mg*dl-1 and 20 mg*dl-1 after oral glucose or ENSO 16, respectively. Insulin and C-peptide AUC0-180 min were significantly greater after glucose compared to ENSO 16 intake (p < 0.01, Wilcoxon rank sum test). The mean maximal concentrations of plasma glucose, insulin and C-peptide after glucose intake were 1.5, 4.6 and 2.7-fold greater after glucose intake compared to ENSO 16 intake, respectively. Adverse reactions were mostly mild and not different between treatments. Conclusion. ENSO 16 has only a small impact on plasma glucose metabolism. This may be of interest in a dietary context and may help to reduce calory intake.Trail registration NCT05457400. First registration: 14/07/2022. https://clinicaltrials.gov/study/NCT05457400 .

Low Fat Yoghurts Produced with Different Protein Levels and Alternative Natural Sweeteners.

The food industry is looking for substitutes for sucrose in food items due to the excessive consumption of products with added sugar and the demand for healthier products. Alternative natural sweeteners can help achieve this goal. Different types of low-fat yoghurts (1% fat), with low-protein and high-protein levels (3% and 4.5-6.5% protein, respectively), were produced using alternative natural sweeteners. The low-protein yoghurts were made with stevia (0.03% w/w) or agave syrup (4.5% w/w). The high-protein yoghurts were made with stevia (0.04% w/w), xylitol (6% w/w) or honey (6% w/w). Sucrose (6% w/w) was used as a control in both trials. pH and titratable acidity, CIEL*a*b* color parameters, syneresis index, rheology and the texture profile of the low-fat yoghurts were evaluated over refrigerated storage. All products underwent sensory evaluation by an untrained panel. The high-protein yoghurts were found to be more acidic (>1% as lactic acid), had a lower syneresis index (between 2.1 and 16.2%) and a better consistency (stronger gel structure) than the low-protein yoghurts. In terms of rheological parameters, stevia-sweetened yoghurts scored higher than the other sweetened yoghurts, showing a better gel structure. The different sweeteners tested did not significantly affect the sensory properties of the yoghurts, although the high-protein yoghurts scored higher for most of the attributes evaluated. Overall, consumers preferred stevia-sweetened yoghurts to yoghurts sweetened with sucrose or agave for the low-protein yoghurts. Of the tested formulations, those containing high protein with the alternative natural sweetener xylitol received higher scores in all attributes. These results reveal the potential of the tested natural sweeteners as sucrose substitutes, while contributing to improving the nutritional value of yoghurts.

Sweet-Tasting Natural Proteins Brazzein and Monellin: Safe Sugar Substitutes for the Food Industry.

This article presents the results of a comprehensive toxicity assessment of brazzein and monellin, yeast-produced recombinant sweet-tasting proteins. Excessive sugar consumption is one of the leading dietary and nutritional problems in the world, resulting in health complications such as obesity, high blood pressure, and cardiovascular disease. Although artificial small-molecule sweeteners widely replace sugar in food, their safety and long-term health effects remain debatable. Many sweet-tasting proteins, including thaumatin, miraculin, pentadin, curculin, mabinlin, brazzein, and monellin have been found in tropical plants. These proteins, such as brazzein and monellin, are thousands-fold sweeter than sucrose. Multiple reports have presented preparations of recombinant sweet-tasting proteins. A thorough and comprehensive assessment of their toxicity and safety is necessary to introduce and apply sweet-tasting proteins in the food industry. We experimentally assessed acute, subchronic, and chronic toxicity effects, as well as allergenic and mutagenic properties of recombinant brazzein and monellin. Our study was performed on three mammalian species (mice, rats, and guinea pigs). Assessment of animals' physiological, biochemical, hematological, morphological, and behavioral indices allows us to assert that monellin and brazzein are safe and nontoxic for the mammalian organism, which opens vast opportunities for their application in the food industry as sugar alternatives.

Sensory profiling of natural sweeteners and sucrose-sweetener binary mixtures.

Overconsumption of added sugars is associated with higher incidences of obesity, type II diabetes, and cardiovascular disease. Alternative sweeteners have long been relied on as a strategy to reduce consumption of added sugars; however these alternatives differ notably from sucrose in their sensory properties. Recently, consumers have also been looking to reduce consumption of ingredients deemed "artificial," seeking natural alternatives despite poor definitions of these terms on the whole. Wider knowledge of the sensory properties of natural sweeteners would greatly aid in this goal. Descriptive analysis and time-intensity scaling were used to characterize the temporal profile and off-flavors of allulose, erythritol, rebaudioside (Reb) A, Reb D, Reb M, monk fruit, and thaumatin, as compared to sucrose. Further, each was blended to reduce sucrose by 50% and 75% in binary mixtures. Where significant off-flavors were frequently reported with sweeteners, when delivered in binary mixtures for partial sugar reduction, these were much mitigated, while also bringing temporal profiles closer to that of sucrose. This suggests that partial sugar reduction may be an effective way of reducing caloric intake while not compromising sensory experience. PRACTICAL APPLICATION: The use of both descriptive analysis and time-intensity scaling allows for a more complete understanding of the sensory properties of natural alternative sweeteners. Understanding their sensory deficits and ways to improve these sweeteners plays a critical role in creating healthier products that will be accepted by consumers.

Use of coconut sugar as an alternative agent in osmotic dehydration of strawberries.

This study aimed to evaluate coconut sugar (CS) as an alternative osmotic agent to sucrose for the osmotic dehydration (OD) of strawberries. OD was performed by immersing strawberries cut into 13.6 ± 0.4 mm edge cubes in osmotic solutions of CS or sucrose, at two different concentrations (40% and 60%, w/w), with and without application of vacuum (AV) in the first 20 min of the process. The total OD time was 300 min. Evaluations of the kinetics of solid gain (SG), water loss (WL), and weight reduction (WR) were performed at 30, 60, 120, 180, 240, and 300 min. SG, WL, and WR increased over the OD time and showed values of up to 7.94%, 63.40%, and 55.94%, respectively. AV increased WL, WR, shrinkage, pH, and total color difference and decreased anthocyanin, ascorbic acid (AA), phenolic, and antioxidant contents. The higher concentration led to higher SG, WL, WR, shrinkage, hardness, and lower moisture content, water activity, anthocyanin, AA, phenolic, and antioxidant contents. The use of CS instead of sucrose had little influence on strawberry properties, except pH and color responses. The optimal treatment was using a 60% CS solution without AV, showing a very distinct color change, hardness increased by approximately 4.5 times and maintenance of acidity, anthocyanins, AA, total phenolics, and antioxidants of 38.0%, 39.6%, 11.8%, 30.0%, 31.1%, and 30.3%, respectively, compared to fresh strawberries. PRACTICAL APPLICATION: Osmotic dehydration of fruit is a process traditionally carried out using sucrose. However, increasing health concerns have made consumers seek alternative sugars to sucrose. The use of coconut sugar made it possible to produce osmo-dehydrated strawberries different from the traditional one, maintaining product quality and process efficiency.

Identification, Chemical Synthesis, and Sweetness Evaluation of Rhamnose or Xylose Containing Steviol Glycosides of Stevia (Stevia rebaudiana) Leaves.

Steviol glycosides obtained from Stevia rebaudiana leaves are increasingly used in the food industry as natural low-calorie sweeteners. Among them, the sweetness of major glycosides composed of glucose residues (e.g., stevioside and rebaudioside A) has been widely studied. However, the properties of minor natural products containing rhamnose or xylose residues are poorly investigated. In this study, five unreported steviol glycosides containing rhamnose or xylose were extracted from our developing stevia leaves, and their sweetness was evaluated. The highly glycosylated steviol glycosides were identified, and their structures were examined by fragmentation analysis using mass spectrometry. Chemical synthesis of these glycosides confirmed their structures and allowed sensory evaluation of minor steviol glycosides. Our study revealed that a xylose-containing glycoside, rebaudioside FX1, exhibits a well-balanced sweetness, and thus, it is a promising candidate for natural sweeteners used in the food industry.

Consumers Respond Positively to the Sensory, Health, and Sustainability Benefits of the Rare Sugar Allulose in Yogurt Formulations.

Increased added sugar consumption is associated with type II diabetes, metabolic syndrome, and cardiovascular disease. Low and no-calorie alternative sweeteners have long been used as an aid in the reduction of added sugar. Unfortunately, these alternative sweeteners often have notable sensory deficits when compared to sucrose. Furthermore, many alternative sweeteners have synthetic origins, while consumers are increasingly turning to foods from natural origins, and from more sustainable sources. Such sweeteners include the rare sugar allulose, which can be manufactured from common agricultural waste and dairy co-product streams, and is reported to have a sensory profile similar to sucrose. This study aimed to determine the influence of the rare sugar allulose on consumer perception of sweetened vanilla yogurt. Participants were recruited to evaluate 4 vanilla yogurts sweetened with either sucrose, allulose, stevia or sucralose, and to rate their liking of the samples overall, and for flavor, texture, and their purchase intent. Statistical analysis of hedonic data from 100 consumers suggested that allulose performed similarly to sucrose in liking and purchase intent, and superior to other sweeteners tested in this study, with fewer off-flavors. Moreover, when consumers were queried on their purchase intent after learning details on the sweetener for each formulation, allulose scored significantly higher than all other formulations in purchase intent. This study highlights the potential of the rare sugar allulose as a low calorie, zero glycemic index, natural and better tasting sugar replacement in sweetened yogurt.

Do the Colors of the Label and the Sweetening Agent Information Influence the Sensory Expectations Consumer? A Case Study with Skyr-Type Yogurt.

The objective of this research was to evaluate the sensory expectation and buying intention of consumers from different Brazilian regions for skyr-type yogurt based on the colors and sweetener on its label. Ten images of skyr mango yogurt labels were created varying in color (orange, white, yellow, blue, and green) and sweetening agent (sucrose and natural sweeteners). Consumers (151 consumers) were asked to rate their expectation for the ideal of sweetness, healthiness, acceptance, and buying intention. Labels containing the information "sweetened with sucrose" had a higher percentage of expectation of sweeter than ideal. Label color and sweetening agent had a significant effect on the expectation of acceptance, with a higher percentage for yogurt sweetened with natural sweeteners. There were not statistical differences (p > 0.05) between the labels regarding expected healthiness. Results also showed that consumers had a low level of familiarity with skyr-type yogurts, but it is presented as a healthy yogurt alternative.

Bioprospecting and biotechnological insights into sweet-tasting proteins by microbial hosts-a review.

Owing to various undesirable health effects of sugar overconsumption, joint efforts are being made by industrial sectors and regulatory authorities to reduce sugar consumption practices, worldwide. Artificial sweeteners are considered potential substitutes in several products, e.g., sugar alcohols (polyols), high-fructose corn syrup, powdered drink mixes, and other beverages. Nevertheless, their long-standing health effects continue to be debatable. Consequently, growing interest has been shifted in producing non-caloric sweetenersfrom renewable resources to meet consumers' dietary requirements. Except for the lysozyme protein, various sweet proteins including thaumatin, mabinlin, brazzein, monellin, miraculin, pentadin, and curculin have been identified in tropical plants. Given the high cost and challenging extortion of natural resources, producing these sweet proteins using engineered microbial hosts, such as Yarrowia lipolytica, Pichia pastoris, Hansenula polymorpha, Candida boidinii, Arxula adeninivorans, Pichia methanolica, Saccharomyces cerevisiae, and Kluyveromyces lactis represents an appealing choice. Engineering techniques can be applied for large-scale biosynthesis of proteins, which can be used in biopharmaceutical, food, diagnostic, and medicine industries. Nevertheless, extensive work needs to be undertaken to address technical challenges in microbial production of sweet-tasting proteins in bulk. This review spotlights historical aspects, physicochemical properties (taste, safety, stability, solubility, and cost), and recombinant biosynthesis of sweet proteins. Moreover, future opportunities for process improvement based on metabolic engineering strategies are also discussed.

Natural sweeteners: Sources, extraction and current uses in foods and food industries.

Food producers have leaned towards alternative natural and synthetic sweeteners in food formulations to satisfy market demands. Even so, several synthetic sweeteners (e.g., aspartame, saccharin, sucralose) are becoming less popular due to health-related concerns, lower nutritional values, and controversies around their safety. Conversely, natural sweeteners confer favourable customer perceptions due to their association to a healthier lifestyle and higher nutritional values. This article discusses the evidence of natural sweeteners in the available commercial products. A comprehensive review of natural sweeteners is presented, which includes their resources, properties and extraction methods, as well as a discussion on several emerging technologies that offer improvements to the traditional extraction methods. Finally, the progress of natural sweeteners in the food industry is assessed, and the commercial food products containing these natural sweeteners are mentioned.

Process Simulation and Techno-Economic Analysis of Large-Scale Bioproduction of Sweet Protein Thaumatin II.

There are currently worldwide efforts to reduce sugar intake due to the various adverse health effects linked with the overconsumption of sugars. Artificial sweeteners have been used as an alternative to nutritive sugars in numerous applications; however, their long-term effects on human health remain controversial. This led to a shift in consumer preference towards non-caloric sweeteners from natural sources. Thaumatins are a class of intensely sweet proteins found in arils of the fruits of the West-African plant Thaumatococcus daniellii. Thaumatins' current production method through aqueous extraction from this plant and uncertainty of the harvest from tropical rainforests limits its supply while the demand is increasing. Despite successful recombinant expression of the protein in several organisms, no large-scale bioproduction facilities exist. We present preliminary process design, process simulation, and economic analysis for a large-scale (50 metric tons/year) production of a thaumatin II variant using several different molecular farming platforms.