CCH_SOME more medical Abbreviations

Abbreviations
ACE angiotensin-converting enzyme
ActRIIB activin receptor IIB
ALK activin receptor-like kinase
Atg autophagy-related genes
atrogin-1 atrophy gene-1
BCAA branched chain amino acid
CR caloric restriction
DHEA dehydroepiandrosterone
DMD Duchenne muscular dystrophy
eIF eukaryotic initiation factor
4E-BP eIF 4E binding protein
FOXO forkhead box O
GH growth hormone
GSK glycogen synthase kinase
IGF-I insulin-like growth factor-I
IL interleukin
JAK Janus kinase
KO knockout
MRTF myocardin-related transcription factor
mTOR mammalian target of rapamycin
mTORC mTOR signaling complex
MuRF muscle ring-finger protein
NF-κB nuclear factor-kappaB
NMJ neuromuscular junction
PGC-1α peroxisome proliferator-activated receptor γ coactivator 1α
PI3-K phosphatidylinositol 3-kinase
p70S6K p70 ribosomal protein S6 kinase
RDA recommended dietary allowance
Rheb Ras homolog enriched in brain
ROS reactive oxidative species
SRF serum response factor
STARS striated muscle activators of Rho signaling
STAT signal transducer and activator of transcription
TNF-α tumor necrosis factor-α
TSC tuberous sclerosis complex
UPS ubiquitin-proteasome system

“Taste is king,” “I mean, the healthiest product in the world really isn’t relevant if people don’t enjoy the taste.”

the relatively low price of sweeteners makes them a valuable commodity as raw material costs relative to the cost of end products, such as carbonated beverages, are high. The comparatively low cost for the finished product makes them a financially accessible item, making them proportionately high in the diet profile of low-income households. The proliferation and easy access to these sugar-rich foodstuffs have provided calorie-rich, but nutrient poor, foods at low monetary, but high public health costs.

To make a cup of Coca-Cola, you’d need much more: about six teaspoons’ worth of sugar, for a 10.4 percent solution. (Pepsi is a little sweeter, at 11 percent. Root beers and some fruit-flavored sodas can be 12 percent or more.) That’s where many substitutes fall short.

Burgeoning demand by a health-aware public for non-caloric, non-glycemic sweeteners resulted in the production of many artificial, non-metabolized sweeteners such as saccharin (from coal tar) and cyclamate (from cyclohexamine) to sucralose (Splenda), which fulfilled the need for a time. Early artificially synthesized sweeteners such as saccharin (synthesized in 1879 from coal tar), cyclamate (synthesized in 1937 from cyclohexylamine), and aspartame (synthesized in 1965) were small molecules with molar masses of about 183, 201, and 294 g/mol, which are similar to the masses of glucose (180 g/mol) and sucrose (360 g/mol) (see Fig. 1). Because of concerns about aftertaste, natural and artificial sweeteners were blended to improve taste and potency . Artificial sweeteners do not trigger insulin production but had other problems such as potential carcinogenicity or metabolism to potentially toxic chemicals ; animal studies linked some artificial sweeteners to cancer  and alteration of gut microbiota . Note that sugar, glucose, fructose, and other naturally occurring sweet carbohydrates are D-sugars, but L-sugars also have sweetness without being metabolized by the body. Public health concerns about the potential for toxicity of artificial sweeteners are somewhat exaggerated (http://www.cancer.gov/about-cancer/causes-prevention/ risk/diet/artificial-sweeteners-fact-sheet). Nonetheless, negative public perception Fig. 1 Structures of the synthetic sweeteners saccharin and cyclamate 2 Brazzein: A Natural Sweetener 19 about nonfood origin synthetic sweeteners spurred the search for natural sweeteners with low glycemic indices [13]. Attention turned to the identification of natural sweeteners from plants used historically by indigenous populations. Their safe use over many generations indicates they may pass regulatory muster by the FDA and be approved for commercial use more rapidly than synthetic compounds.

At present, in the United States, five synthetic sweeteners are now permitted, namely, acesulfame-K, aspartame, neotame, saccharin, and sucralose (Duffy and Anderson, 1998; Anonymous, 2002). Neotame, approved only in 2002, is an N-alkylated aspartame derivative, and has a sweetness potency of 10,000 times that of sucrose (Waiters et aL, 2000; Stargel et aL, 2001; Anonymous, 2002). In the United States, the artificial sweeteners are estimated to account for an approximately $720 million market by 2003 (Seewald, 2000). However, problems have been perceived with some of these compounds in terms of their safety, stability, cost, and/or quality of taste. For example, the general-purpose sweetener aspartame may not be consumed by persons with phenylketonuria because of the formation of a major metabolite, phenylalanine (Butchko et al., 2001). Saccharin has been used as a sweetener for many years, but is now permitted only on an interim basis, owing to an association with bladder cancer in laboratory

individual descriptions of potent sweeteners in the categories terpenoids and steroids, phenylpropanoids, dihydroisocoumarins, flavonoids, proanthocyanidins, benzo[b]indeno[1,2- d]pyrans, amino acids, and proteins. The literature has been surveyed for this article until the middle of 2002. The plantderived sweetness modifiers will not be considered further in this review. Commercially used highly sweet natural products While many isolated natural compounds from plants have a sweet taste (Kinghorn and Soejarto, 1986, 1989; Kinghorn et aL, 1995; Kinghorn et aL, 1999), only a few of these have been developed commercially. Natural product highly sweet compounds and compound mixtures with some commercial use include glycyrrhizin (1), mogroside V (2), phyllodulcin (3), rebaudioside A (4), stevioside (5), "sugar-transferred" stevia extract, and thaumatin, which are used as sucrose substitutes   

India/UK firm claims to have first commercially viable scale-up process for brazzein

UK firm claims to have first commercially viable scale-up process for brazzein
By Niamh Michail

22-Jun-2018 - Last updated on 22-Jun-2018 at 14:20 GMT

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Oubli berries contain the sweet-tasting brazzein protein which could be a promising natural sweetener. © iStock Oubli berries contain the sweet-tasting brazzein protein which could be a promising natural sweetener. © iStock

Magellan Life Sciences says its patent-pending fermentation process to scale up the sweet-tasting protein brazzein will make it the first company to market the natural, zero-calorie sweetener.


Brazzein is the name of the sweet-tasting protein that occurs naturally in the West African fruit of the climbing plant, Pentadiplandra brazzeana Baillon​, also known as oubli.

The zero-calorie protein is around 1,500 times sweeter than sugar and has a similar flavour profile to sucrose with no after-taste. However, the oubli fruit

Beyond-stevia-Will-brazzein-make-the-natural-sweeteners-premier-league_large
© C. M. Hladik
is rare and protected by biodiversity laws so extracting it from the fruit is not possible, and scale up has proven difficult.

UK company Magellan Life Sciences has developed a fermentation process that promises commercial quantities of the protein that are ‘nature identical’. Using an FDA-approved microorganism strain and food-grade chemicals to provide carbon and nitrogen sources for the fermentation process.

Although the microorganism is genetically modified (GM), the brazzein does not contain this and the final product could therefore be labelled as GM-free, it said.

“The platform’s industry leading productivity level combined with simplified down-stream processing makes it the first commercially viable and scalable production process for brazzein​,” the company said.

A patent has already been approved by the Indian patent office and is pending in the US, EU and China.

'Significant advantage'
Magellan Life Sciences was founded by husband-and-wife team Dr Abhiram Dukkipati, a biologist and former Stanford University fellow, who is the company’s CEO and Laxmi Wagle, the chief strategy officer.

Dukkipati said: “The end consumer is seeking a sweetener that actually tastes like sugar without any of the off-tastes of stevia. Brazzein is closer in taste to sugar than steviol glycosides. The sheer taste factor puts brazzein at a significant advantage over stevia and most other artificial sweeteners.”  ​

Water-soluble brazzein also withstands typical cooking processes such as high temperatures and freezing and has a range of pH values, making it interesting for food manufacturers.

Scaling-up
So if brazzein really is the holy grail of sugar replacement and has a clean, sucrose-like taste, why has it not already been embraced by the food industry? 

“This is often the question that people ask,” ​Wagle admits. “From the time the molecule was discovered, the University of Wisconsin had a patent on it, and when this expired, a few companies tried to produce it.​

“You can make the molecule in a laboratory but if you want to do it on a commercial scale, you need to be able to produce it in tonnes. That scaling-up process is something people haven’t been able to do. Now we have a process to do that.”​

In 2016, Korean researchers described a method of scaling up brazzein using the kluyveromyces lactis yeast strain​ ​while US-based Natur Research Ingredients​ ​has been working to bring it to market since around 2008.

UK move
The company was established in 2014 in Hyderabad in the couple’s native India but FoodNavigator spoke to Wagle on the day it became a UK limited company – a strategic move that will see its headquarters move to London and a research laboratory and pilot plant to Norwich.

“Science in India is still in nascent stage and it can be difficult to get funding or attract foreign investment there,” ​said Wagle. “People in the West are also more accepting of new molecules on the market, so this is another reason why we wanted to move.”​

Interest has been growing. In January this year, it was selected for the Rebel Bio accelerator program and in 2017, won Danish biotech supplier Novozymes’ Scicube open innovation challenge.

It has also received funding from life sciences investment firm, SOSV.

Next steps​
The next steps are scaling up production in the UK site and preparing the paperwork and necessary studies to get the product approved for the market. The company will be applying to the US Food and Drug Administration for Generally Recognised as Safe (GRAS) status and submitting a request for a scientific opinion to the European Food Safety Authority (EFSA). 

Based on conservative estimates from regulatory consultants, Wagle said they expect to be approved in around one and a half years.

It is not yet clear how the sweetener could be labelled on pack but Dukkipati is confident that “since brazzein actually occurs in nature, we would most likely label it as a ‘natural’ sweetener”.​

While it is too early to have an idea of its cost, Wagle said she expects it to be “as competitive as premium quality stevia​” which retails for around $300 per kilo, “if not more so​”.

“Another advantage is that 1 kg of stevia is equivalent to 250 g of brazzein so the cost-in-use could be lower.”​

Magellan Life Sciences is currently conducting trials with food companies to explore its functionality, such as bulking properties.

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Brazzein entrepreneur seeks partner to take next-generation natural sweetener to market By Elaine WATSON


Brazzein - a protein from the berry of the West African plant Oubli claimed to be 2,500+ times sweeter than sucrose - could play a key role in the natural sweeteners market in future as formulators look beyond stevia, says one entrepreneur intent on commercializing it.

Brazzein - a protein from the berry of the West African plant Oubli claimed to be 2.500+ times sweeter than sucrose - could play a key role in the natural sweeteners market in future as formulators look beyond stevia, says one entrepreneur intent on commercializing it." Loren Miles, CEO of LA-based Natur Research Ingredients, has been trying to get brazzein to market for some years and admits it's taken longer than he original\y envisaged, in part because industry attention has been on stevia. "Everyone fell in love with stevia, and it also had a shorter timeline [to get to market), so the big players bet big on it," he told FoodNavigator-USA this week. "Bat there is an aftertaste." Whereas "monk fruit has a juicy-fruit-type candy taste profile and stevia has a licorice aftertaste", brazzein has more of a "sucrose-type profile that makes it easier for formulators to use", said Miles. And as firms exp\ore other natural sweeteners, brazzein (from the fruit of the climbing plant Pentaäiplandra brazzeaaa Baillon) ticks many of the right boxes, he claimed,