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Q: for tehuti-ga. Fermentation based nutritional supplements ( Answered 4 out of 5 stars,   0 Comments )
Subject: for tehuti-ga. Fermentation based nutritional supplements
Category: Science > Chemistry
Asked by: blucken-ga
List Price: $100.00
Posted: 01 Aug 2003 06:50 PDT
Expires: 31 Aug 2003 06:50 PDT
Question ID: 237735
Could you provide a list of the raw material nutritional supplements/
nutraceuticals products that are manufactured via a fermentation route
or process.

Request for Question Clarification by tehuti-ga on 13 Aug 2003 14:40 PDT
Hello blucken,

I'm sorry, but I have only just now seen this question addressed by
you to me. Do you still wish me to tackle it?

Clarification of Question by blucken-ga on 13 Aug 2003 20:09 PDT
Subject: Re: for tehuti-ga. Fermentation based nutritional supplements
Answered By: tehuti-ga on 14 Aug 2003 09:04 PDT
Rated:4 out of 5 stars
Hello blucken,

Apologies once more for missing your question when it first appeared.
I had gone away from home the day before and did not return until
August 3, by which time the question had slipped out of the first
pages. Unfortunately, we do not receive automatic notification of
questions, even if they are aimed at a specific researcher, although
we do get notified of clarification requests on our answers.

I have looked at current uses of fermentation, and also at processes
that are still in development.

1. Chitin, chitosan and glucosamine  (I’ve included these because I’m
not sure if I listed these manufacturers in my previous answers.
Otherwise, I have tried not to repeat information supplied previously)
“APT Inc. has developed a proprietary bacterial fermentation process
with partners from the United States and the United Kingdom for
extracting chitin from shellfish waste.”
“Basic grade chitin can be derived from crustacean waste using our
proprietary fermentation process. Higher grade chitin for
neutraceutical uses and medical applications are under development.
…  Glucosamine.  Research is under way to produce glucosamine using a
modified version of our fermentation process.
Chitosan. We are exploring options for extracting chitosan as part of
our product line.”
Applied Preservation Technologies, Canada, web site

“January 7, 2003 – Bio-Technical Resources (BTR), a division of Arkion
Life Sciences LLC, today announced it is commercializing its
technology to produce glucosamine by microbial fermentation, with
product availability in the first quarter of 2003. “
The web page includes a summary of the following presentation:
E. coli Metabolic Engineering and Fermentation for Industrial
Production of Glucosamine
Ming-De Deng, Sarah Wassink, Al Grund, Dave Severson, Jeff Running,
Candice Leanna, Linsheng Song, Kathy Nielsen, Bonnie Walsh, Brian
Huckins, Rich Burlingame 

2. Single Cell Oils (microbial oils) - polyunsaturated fatty acids
Extracts from the abstracts of presentations at the 94th AOCS
(American Oil Chemists' Society)Annual Meeting, Kansas City, May 2003 

a. Single Cell Oils in the 21st Century. 
C. Ratledge, University of Hull, UK.
“It was not until there was a need for specific polyunsaturated fatty
acids as dietary supplements, especially for premature and neonatal
babies, that SCOs came into prominence. …. established the value of
incorporating arachidonic acid (ARA) and docosahexaenoic acid (DHA)
into infant formulae  … benefits of using PUFAs, including DHA and EPA
(eicosapentaenoic acid), for the treatment of a range of clinical
conditions, including schizophrenia, bipolar disorder and even certain
cancers. Increased demand for PUFAs for the prevention of cardiac
disease  …  the very long chain PUFAs, such as ARA, EPA and DHA, can
only be produced using microorganisms and today large-scale commercial
processes for ARA and DHA production now operate in the USA, Japan and
Europe. Increased demand for other PUFAs, including EPA, is expected
to increase further the interest in SCOs.”
b. Large-scale Production of Several Unique PUFAs by Mutants of an
Arachidonic Acid-producing Fungus Mortierella alpina 1S-4. S. Shimizu,
E. Sakuradani and J. Ogawa, Graduate School of Agriculture, Kyoto
University, Japan.
“The C20 polyunsaturated fatty acids (PUFAs) of n-6, n-3 and n-9 have
been versatile and unique biological activities. These PUFAs or lipids
containing them are of highly potential in neutraceutical and
pharmaceutical applications…. Various kinds of M. alpina mutants…  
Some of these mutants operate new pathways of PUFA biosynthesis. ….
the resultant mycelia are a rich source of novel triacylglycerol
composed of n-9 PUFAs.”

c. Development of a DHA Production Technology Using Schizochytrium: A
Historical Perspective.
W. Barclay, C. Weaver and J. Metz, Martek Biosciences Boulder, USA.
“A fermentation-based production technology was developed using
Schizochytrium. Schizochytrium is a member of the Stramenopiles, most
closely related to the golden algae. The key production strain was
isolated using a bio-rationale collection/screening program designed
to isolate an “ideal” microorganism for production of DHA in

d. Production of Long Chain Polyunsaturated Fatty Acids (LC-PUFAs) by
Z. Cohen, I . Khozin-Goldberg and P. Shrestha, J. Blaustein Institute
for Desert Research, Ben Gurion University, Israel.
“Our studies on the red microalga Porphyridium cruentum have shown
that LC-PUFAs accumulated in TAG [triglycerols], can be utilized for
the rapid biosynthesis of the eukaryotic-like molecular species of
chloroplastic lipids at low temperatures…. isolated a microalga that
was identified as the chlorophyte (trebouxiophyceae) Parietochloris
incisa. This alga was found to be the richest plant source of the
pharmaceutically valuable LC-PUFA, arachidonic acid… “

e. Commercial Production of Arachidonic Acid-containing Oil with
Mortierella alpina.
H. Streekstra, J.H. van Doesum and B. Schulze, DSM Food Specialties,
the Netherlands
“this is the first fungal edible oil with a sustained commercial
potential. It is running in full-scale fermentation and
downstream-processing facilities, and has done so for a number of
years. Arachidonic acid being an ingredient for infant formula, high
demands are made on product quality and consistency, more so because
of the chemical sensitivity of highly unsaturated oils. A
fermentation-based process in closed systems provides an excellent
technological platform for producing such a specialty product.”

f. Commercial Production of DHA from Dinoflagellates. 
K. Apt, Martek Biosciences Corp, USA.
“Docosahexanenoic acid (DHA) is an important long chain
polyunsaturated (LCPUFA), omega-3 fatty acid in human nutrition. It is
the major structural fatty acid present in brain, eye and other neural
tissues. There is an extensive market for DHA products based on its
nutritional characteristics
… Martek has developed a GMP process utilizing the microalgae
Crypthecodinium cohnii to produce a single cell oil with a DHA
enrichment of greater than 40%. The organism is cultivated by large
scale fermentation, the biomass is spray dried and the oil extracted
using a process similar to that used for plant oils.”

3. Vitamins
Chapter 11 Vitamins and Related Compounds: Microbial Production
by Sakayu Shimizu
Full text plus diagrams of first 9 pages available in pdf format

From the information available in these 9 pages:

Riboflavin: is produced by both synthetic and fermentation processes,
with major producers being  Hoffmann-La Roche (Switzerland), BASF
(Germany), ADM (USA), Takeda (Japan)].
“Two closely related ascomycete fungi, Eremothecium ashbyii and Ashbya
gossypii, are mainly used for the industrial production
…  Yields much higher than 10 g of riboflavin per liter of culture
broth are obtained in a sterile aerobic submerged fermentation with a
nutrient medium containing molasses or plant oil as a major carbon
source. Yeasts (Candida flaeri, C. famata, etc.) and bacteria can also
be used…
…  Riboflavin production by genetically engineered Bacillus subtilis
and Corynebacterium
ammoniagenes which overexpress genes of the enzymes involved in
riboflavin biosynthesis
reach 4.5 g LP1 and 17.4 g LP1, respectively”

Vit C: Enzymatic conversion of 2,5-(2-Keto-L-gulonic acid)
(Corynebacterium sp.) diketo-D-gluconate obtained through fermentative
process to 2-keto-L-gulonic, followed by chemical
conversion to L-ascorbic acid

Biotin: fermentative production from glucose by a genetically
engineered bacterium or enzymatic
conversion from diaminopimelic acid using the biotin biosynthesis
enzyme system of a mutant of Bacillus sphaericus.

Vitamin B12: fermentative production from glucose by Propionibacterium
shermanii, Pseudomonas denitrificans and other bacteria.
Pyrroloquinoline quinone:  fermentation from methanol by a
methanol-utilizing bacterium.

At there is a
summary of:
Fermentation Process Development for the Production of L-Ascorbic Acid
by the Microalga Prototheca moriformis.
Dave Severson, Jeff Running
“a one-step biological process from glucose”

4. Amino acids

“Varsal, in partnership with a Chinese producer, has expanded the
range of amino acid products they offer. In addition to regular amino
acids, Varsal now offers specialty amino acids and derivatives.
Production of basic amino acids is located in a facility that
specializes in fermentation and enzyme technology. This plant offers
economical production of high quality amino acids through efficiency
in design and operations. The main fermentation products are L-Valine,
L-Leucine, and L-Isoleucine.” (web site of Varsal Inc, a
manufacturer of chemicals)

“Wacker-Chemie has succeeded in producing the amino acid L-cysteine by
fermentation - a real biotechnological challenge! The company has
developed this unique process independently at its central research
facility 'Consortium fuer elektrochemische Industrie' in Munich,
Germany. The process is based on a bacterial strain which has been
'metabolically designed' to synthesize L-cysteine from dextrose.
This is the second fermentation process for an amino acid successfully
developed by Wacker`s biotech experts. In the early 1990s Wacker
developed a fermentation process for L-tryptophan.”
(Wacker-Chemie web site)

“Furthermore, according to a representative from Wacker Biochem, the
process may be regarded as a platform technology targeting new
fermentation processes for nutraceuticals and special amino acids. The
ingredient’s properties as a free-radical scavenger, antioxidant, and
glutathione precursor permit
its use in nutraceuticals as a liver-protecting substance and as an
anti-aging agent. The stereo-selective synthesis of this L-amino acid,
combined with its amino, carboxyl, and sulfhydryl
functional groups, make it a building block for further syntheses.”
From: Timely ingredients developments via fermentation by Donald E
Food Technology, Vol 56 no. 2, February 2002

J. Plachý (Research Institute of Antibiotics and Biotransformations,
Roztoky u Prahy, Czech Republic): Fermentation of amino acids. -
Biologické listy 63 (1): 61-76, 1998.
“The majority of amino acids are now produced by fermentation…  from
simple raw materials…. The most frequent amino acid producers are
mutants of coryneform bacteria represented by the genera
Corynebacterium and Brevibacterium. In addition to mutants of various
type, …   the amino acid producers can be obtained by the methods of
gene manipulation.
… At the present time Japanese companies are chief amino acid
producers in the world.”

5. Fungal polysaccharopeptides (medicinal mushroom products)

Polysaccharopeptides of Coriolus versicolor: physiological activity,
uses, and production
Jian Cui, Yusuf Chisti 
Institute of Technology and Engineering PN456, Massey University,
Private Bag 11 222,
Palmerston North 5320, New Zealand
Biotechnology Advances 21 (2003) 109– 122
Full text:

“The protein-bound polysaccharides or polysaccharopeptides produced by
Coriolus versicolor are
effective immunopotentiators
… Several kinds of protein-bound polysaccharides have been shown to be
produced by the
white rot fungus, C. versicolor. 
…  . In nature, C. versicolor occurs as a mushroom body, but the
fungus can be grown as mycelial biomass in submerged culture in
bioreactors. Mushrooms gathered in the wild, cultivated
mushrooms, and the mycelial biomass of submerged culture are used to
produce the polysaccharopeptides.
… The best known commercial polysaccharopeptide preparations of C.
versicolor are polysaccharopeptide Krestin (PSK) and
polysaccharopeptide PSP. Both products are obtained from the
extraction of C. versicolor mycelia. PSK and PSP are Japanese and
Chinese products, respectively. Both products have similar
physiological activities but are structurally different. PSK and PSP
are produced from CM-101 and Cov-1 strains of C. versicolor,
respectively. Both products are obtained by batch fermentation.
… In addition to clinically tested PSK and PSP, numerous other extract
preparations of C. versicolor are on the market as neutraceuticals and
traditional medicines. Neutraceutical polysaccharopeptide preparations
are sold worldwide in the form of capsules, ground biomass tablets,
syrups, food additives, and teas.”

As well as being immunostimulating and having anticancer activity,
these substances are said to induce production of superoxide
dismutase, improve appetite and liver function, calm the central
nervous system, improve the pain threshold and help in intestinal
disorders. No toxicity has been noticed, even after prolonged use
(except for the obvious fact that the action of these substances would
be undesirable in cases where someone is on immunosuppressants!). The
review covers some of the evidence for these claims that has been
obtained in laboratory studies. It also describes the various
production systems.”

6. Carnitine

Carnitine: “For many years, the only available manufacturing process
consisted of the classical chemical production of DL-Carnitine with
subsequent separation of the D- and L-enantiomers. This
separation inevitably results in some residual D-Carnitine in the
L-Carnitine final product. A
better method, which has been patented by Lonza Ltd, a Swiss
life-science company, is based
on microbial fermentation. It starts from an optically inactive
precursor molecule, using a
biotransformation step for stereoselective introduction of the optical
centre. The most important benefit: this method guarantees production
of optically 100% pure L-Carnitine
without any harmful D-Carnitine.”
Overview of Carnitine (written with the support of Lonza Ltd)

7. Soy isoflavones
“Studies have shown that soy isoflavones such as genistein, daidzein,
and glycitein have a
variety of potential health benefits, and proprietary fermentation
processes can deliver soy products that are even more potent in these
components, offering enhanced value in health and functionality.”
From: Timely ingredients developments via fermentation by Donald E
Food Technology, Vol 56 no. 2, February 2002

“A related project at Fermalogic involves nutraceutical production,
particularly the production of isoflavones as an added-value product
of the erythromycin fermentation. The isoflavones, genistein and
daidzein, come from the soybean component of the fermentation medium.
A serious problem with isoflavone degradation, however, has kept this
process from commercial development .
Recently a collaboration between scientists at Fermalogic, deCODE
genetics pharmaceuticals group, and the University of Minnesota has
identified a key step in the isoflavone degradation pathway. This new
information has helped us to devise a straight-forward method to
optimize the process.” (Fermalogic Inc)

8. Gluconates
“From our fermentation facility in Peoria, Illinois, we produce a wide
variety of forms and packaging to meet the broad range of indstrial
applications for Gluconates.”
“As one of the most readily assimilated forms of calcium in human
metabolism, calcium gluconate is used widely in both human and
veterinary pharmaceuticals to treat calcium deficiency.
… The importance of calcium is also growing in today's
"nutraceutical"market …. Many vitamins, sports drinks and powdered
diet beverage mixes have added calcium.”
“Potassium is an important element in mineral nutrition. It helps
moderate cell fluid levels and promotes osmotic balance in the body.
Its bland flavor and high solubility make potassium gluconate the
ideal choice in supplementing the mineral nutrition of food products.” (PMP Fermentation

9. Carotenoids 

“Fermentative carotenoid production is the subject of U.S. Patent No.
6,291,204, issued September 18, 2001, and assigned to Roche Vitamins,
Inc., Parsippany, N.J. The patent discusses the proteins and DNA
sequences that provide an improved biosynthetic pathway from farnesyl
and isopentyl pyrophosphate to various carotenoids, including
zeaxanthin, astaxanthin, adonixanthin, and canthaxanthin. According to
the patent, more than 600 different carotenoids have been described
from carotenogenic organisms found among bacteria, yeast, fungi, and
plants. Currently, two of them, beta-carotene and astaxanthin, are
commercially produced in microorganisms”
From: Timely ingredients developments via fermentation by Donald E
Food Technology, Vol 56 no. 2, February 2002

10. Diverse nutraceuticals

“In Europe, a large collaborative research project is underway on the
development of nutraceuticals and functional foods through
fermentation of dairy and soy raw materials. The project, referred to
Nutra Cells, is sponsored by the European Commission and coordinated
by Nizo Food Research, P.O. Box 20, 6710 BA Ede, The Netherlands
(phone 31-318-659511; fax 31-318-650400; The project,
which will run for a period of four years, focuses on the formation
of health-promoting components in food as a result of bacterial
From: Timely ingredients developments via fermentation by Donald E
Food Technology, Vol 56 no. 2, February 2002

“The health-status of the food products will be greatly improved by
either production or addition of components such as
low-calorie-sugars, oligosaccharides or B-type vitamins, or by removal
of undesirable food components such as lactose, galactose and
raffinose. The nutraceuticals will be produced by lactic acid
bacteria, propionic acid bacteria and bifidobacteria, all with a
secure record of safe use in the food industry. The
nutraceutical-generating activity will be enhanced in these food-grade
micro-organisms either by selection of optimal strains and
fermentation conditions or by food-grade modification of metabolism in
these strains.”
From a web site giving an overview of the project at 

11. D-ribose
“After exercise, ATP stores are depleted…  Recovery times can be
significantly enhanced, however, by bypassing the time-consuming
biochemical pathways that restore ATP…. pump-prime the body directly
with the precursors of ATP. D-ribose is a sugar molecule that provides
a fundamental building block of ATP. … Since its founding in 1996,
Minneapolis-based Bioenergy Inc. has amassed clinical studies and
patents to support the role its trademarked Bioenergy Ribose plays in
recovery processes, be it sports recovery or surgical trauma recovery.
Research under way even suggests a positive role for D-ribose in the
alleviation of chronic fatigue syndrome. The company manufactures
D-ribose via fermentation.”
From: Sports beverages follow road to recovery by Daniel Best

12. S-adenosyl methionine
“A new process, which utilizes an engineered strain of yeast”.
“SAM is an important metabolite formed from methionine and adenosine
triphosphate (ATP), and is active in many cellular reactions, serving
as a universal methyl donor.”
“Provides a simple fermentation process for the production of SAM
Low cost. Eliminates the need to supply the costly precursor,
Produces only the active stereo isomer of SAM”
“SAM is available as an over-the-counter dietary supplement, and has
been used in the treatment of depression, osteoarthritis,
fibromyalgia, liver disease, and migraine headaches.”
“This technology has been developed at the Department of Chemistry and
Biochemistry of the University of Texas at Austin and the Department
of Horticultural Sciences at the University of Florida at Gainesville.
It is being offered to industry as either a stand-alone license
opportunity or in conjunction with a sponsored research agreement for
development of the specific application areas as described above. A
patent application is pending.” 

13. Chondroitin
“Choncept is a biotech company focused on development of new
technology to produce chondroitin from fermentation of recombinant
bacteria to replace the current chondroitin source of beef and other
animal by-products. Chondroitin produced by the gene patented by
Choncept is unsulfated which can be sulfated to produce chondroitin
similar to that isolated from animal sources.” 

14 FPP – Fermented Papaya Product
“FPP is a nutraceutical produced by  yeast fermentation of Carica
papaya and  (Osato Internat., Gifu , Japan ).  FPP consists of oligo-
and monosaccharides, oligopeptides and amino acids, SH-containing
compounds, retinoic acid and so on.  In a number of experimental
studies FPP was found to be a free radical scavenger, inhibitor of
lipid peroxidation, chelator of transition metals, and suppressor of
free radical-associated pathologies in animals.  Since FPP was
approved as a healthy food additive in Russia  and Ukraine , we have
performed several clinical trials attempting to show a correlation
between the FPP beneficial clinical effects and its capacity to
modulate oxidant/antioxidant balance in the body.”
Oxidant/Antioxidant Modulating Activity of FPP (Fermented Papaya
Preparation) and its Clinical Efficacy
L. Korkina,  Afanaslev, and J.A. Osato 

15. D-proline, L-Hydroxyproline, N-Acetyl-L-Hydroxyproline 
Advertised as being produced by fermentation on Kyowa-Hakku web site

16. Probiotic bacteria

17 Enzymes

“a safer and effective alternative to animal pancreatin. The three
principal enzymes are: Lipase (fat splitting), Amylase (starch
liquefying), and Protease (protein solubilizing) which are obtained
from the fermentation of Aspergillus oryzae and Aspergillus niger.”
Advertisement at

“Using enzymes that cleave the beta-ether linkage between the
isoflavone and glucose molecule would enable the gut to take up the
genistein and daidzein. This idea is the crux of Isolase™, a
patent-pending enzyme system developed by National Enzyme Co. (NEC)
and produced through controlled fermentation of Trichoderma

Search strategy
nutraceutical fermentation process
neutraceutical fermentation process 
nutraceutical “produced by” fermentation
fermentation "dietary supplement"
plus searches on individual terms discovered through the above
blucken-ga rated this answer:4 out of 5 stars and gave an additional tip of: $5.00

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