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[SANET-MG] gm crops fpr health? part 4
part 4
gm crops for health
Peptides both natural and synthetic
Glutathione (GSH) is an antioxidant consisting of three amino acids that
protects cells from free radicals and participates in metabolic
reaction. GSH is the most abundant low molecular weight thiol (compounds
with -SH group) in plants. It accumulates to high concentrations
particularly in response to stress. A bacterial enzyme catalyzing
glutathione synthesis and lacking feed back inhibition was used to
enhance glutathione production in plants [83]. Glutathione is important
in maintaining nutritional homeostasis and great caution must be
exercised in manipulating glutathione levels in plants. Increasing
glutathione levels in tobacco unexpectedly resulted in continuous
oxidative stress in the plants [84].
Anti-microbial peptides provide the first line of defence against
invading bacteria, fungi and viruses in both plants and animals and are
part of the host’s innate immunity, acting mainly at the cell membrane.
They are 15 to 40 amino acids in length, most of them hydrophobic
(water-hating) and cationic (positively charged), and are beginning to
find applications in medicine and in crop protection.
A synthetic peptide D4E1 based on the cecropin B peptide toxin (obtained
from the moth, Cecropia), consists of a linear sequence of 17 amino
acids: FKLRAKIKVRLRAKIKL (F for phenylalanine, K for lysine, L for
leucine, R for arginine, A for alanine, I for isoleucine, V for valine).
The peptide protected against Aspergillus and Fusarium fungi. It acts by
binding to ergosterol, a sterol present in fungal cell walls [85]. On
further tests, D4E1 was found to have broad-spectrum anti-microbial
action, and was active against fungi belonging to the orders Ascomycete,
Basidiomycete, Deuteromycete and Oomycetes, as well as bacterial
pathogens Psuedomonas and Xanthomonas [86]. The D4E1 toxin also proved
effective in treating Chlamydia infection in humans [87]. Synthetic
peptides of 11 amino acids proved effective against bacterial plant
pathogens, with minimal cytotoxicity and protease degradation, offering
improved crop protection as an external pesticide or incorporated into
transgenic crops [88].
A DNA sequence encoding synthetic peptide 10 amino acids long replaced
the active region of the tomato prostemin gene in order to enhance
production and processing of the peptide. The hybrid gene facilitated
the transfer and insertion of the peptide into tobacco plants where it
proved active against microbial pests [89].
Researchers at the National Agricultural Research Center, Niigata,
Japan, have created transgenic rice with the anti-microbial peptide
defensin from Brassica. The transgenic rice plants were resistant to
rice blast disease caused by the fungus Magnaporthe grisea. The
researchers then systematically altered the genetic code for defensin to
produce synthetic peptides that were far more toxic to the fungus than
the natural peptides [90]. Rice with the synthetic genes and peptides
are being proposed for field-testing prior to commercial release in Japan.
A potato virus X expression system was used to produce a killer peptide
derived from a single chain anti-idiotype antibody of a broad spectrum
microbiocidal yeast killer toxin with a strong activity against human
pathogens. The killer peptide was tested against both bacterial and
fungal plant pathogens and proved very effective. The killer toxin was
fused to the virus X coat protein in a system that allowed its rapid
production [91]. The virus production system is capable of spreading the
toxin to potato, for better or for worse.
There have been criticism and objections to open field-testing of crops
modified with the synthetic peptides. The evolution of resistance to
anti-microbial peptides will severely compromise both the natural
defence of the human immune system against disease and the possibilities
of effective therapies emerging in the wake of the disaster of
widespread antibiotic resistance [92] (No to Releases of Transgenic
Plants with Antimicrobial Peptides). As versions of the peptides also
provide defence against pathogens in other animals and plants, the
ecological impact of resistant pathogens could be devastating. Another
factor adding to the hazards to health and the environment is that the
synthetic transgenes code for peptides that are significantly different
from the natural versions. This may itself be responsible for toxic or
other harmful effects that cannot be known unless thoroughly tested.
Genetically modified microbes in food
Probiotic microbes including Lactobacillus species, Bifidobacterium
species and the yeast Saccharomyces boulardii, have been used as food
supplement. The health benefits of probiotic microbes include
antagonistic effects on gastroenteric pathogens, neutralisation of food
mutagens produced in the colon, shifting the immune system to alleviate
allergy and lowering serum cholesterol [93] (Health-promoting Germs).
Probiotic microbes are being developed as vectors for gene therapy and
genetically modified to “improve” the quality of food.
The probiotic lactic acid bacteria have been extensively modified to
serve the food industry and other purposes. Modifications included
modulation of the proteolytic system to enhance cheese ripening,
increasing the production of the Kreb’s cycle enzyme alpha keto
glutarate, using antisense RNA to silence lytic Lactoccocus phage,
introducing a folate gene cluster, re-routing pyruvate to L-alanine, and
over-expressing the riboflavin biosynthesis pathway. Further genetic
modifications of lactic acid bacteria involved inactivation of glucose
fermentation and introduction of lactose fermentation, introduction of
alpha-galactosidase, of phytase, of alpha amylase and cellulose. Lactic
acid bacteria have also been genetically modified with bacteriocin toxin
to prevent dental carries; for increased activity of beta-galactosidase,
for lacticin (a bacteriocin) production, for increased nicin production,
and increased proteolytic and acidifying activity. The probiotic
bacteria have been enhanced for glutathione production, and for
oxidative stress tolerance. Lysostaphin, a glycylglycine endopeptidase
that specifically cleaves the pentaglycine cross-bridges found in the
staphylococcal peptidoglycan was inserted into lactic acid bacteria for
use in destroying the pathogen. The safety assessment and regulation of
these GM probiotic bacteria were discussed in recent reviews [94, 95].
The production of nutraceuticals (foods or components with health
benefits) with genetically modified food grade microbes and their safety
assessment were also reviewed [96]. GM probiotic bacteria have not
received much public scrutiny mainly because the regulation of such
microbes is separate from the regulation of GM crops. There is a strong
likelihood that GM probiotic bacteria may be introduced to the market
before serious safety concerns are addressed.
Using GM probiotic bacteria requires special caution. These bacteria are
natural symbionts of the gastrointestinal tract, and have adapted to
their human and animal hosts over millions if not billions of years of
evolution. Genetically modifying them could easily turn them into
pathogens pre-adapted to invade the human and animal gut [97].
Furthermore, the gastroinstestinal tract is an ideal environment for
horizontal gene transfer and recombination, the major route to creating
pathogens. For these reasons, we have proposed that any genetic
modification of probiotic bacteria should be banned [98, 99] (Ban GM
Probiotics; GM Probiotic Bacteria in Gene Therapy).
Fowls grew faster when fed transgenic yeast Pichia pastoris modified
with a pig growth hormone gene with an alcohol oxidase promoter and an
alpha-factor signal peptide. The modified yeast mixed with the fowl diet
made the fowl grow about 10 percent faster than controls [100]. Growth
hormone food microbes may be attractive for chicken farmers, but their
use may carry the microbes over into the human population; and not
everyone would want to grow like pigs.
Microbial bio-control agents have been developed and the impact of such
agents on foods requires careful consideration. A modified Trichoderma
atroviride with a glucose oxidase gene from Aspergilus niger rapidly
overgrew and lysed the plant pathogens Rhizoctonia solani and Pythium
ultimum. The transgenic bio-control agent both defeated the pathogens
and induced systemic resistance in treated plants [101], but they should
be studied extensively for their impact on food safety and quality.
The modification of food microbes requires comprehensive public scrutiny
especially as numerous modified strains are awaiting release into the
commercial markets.
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