https://www.cell.com/trends/biotechnology/pdf/S0167-7799(01)01739-5.pdf

The 'biodrug' concept : an innovative approach to therapy

The use of genetically engineered microorganisms such as bacteria or yeasts as live vehicles to carry out bioconversion directly in the digestive environment is an important challenge for the development of innovative biodrugs. A system that mimics the human gastrointestinal tract was combined with a computer simulation to evaluate the survival rate and cinnamate 4-hydroxylase activity of a recombinant model of Saccharomyces cerevisiae expressing the plant P450 73A1. The yeasts showed a high level of resistance to gastric and small intestinal secretions (survival rate after 4 h of digestion, 95.6% ± 10.1% [n = 4]) but were more sensitive to the colonic conditions (survival rate after 4 h of incubation, 35.9% ± 2.7% [n = 3]). For the first time, the ability of recombinant S. cerevisiae to carry out a bioconversion reaction has been demonstrated throughout the gastrointestinal tract. In the gastric-small intestinal system, 41.0% ± 5.8% (n = 3) of the ingested transcinnamic acid was converted into p-coumaric acid after 4 h of digestion, as well as 8.9% ± 1.6% (n = 3) in the stomach, 13.8% ± 3.3% (n = 3) in the duodenum, 11.8% ± 3.4% (n = 3) in the jejunum, and 6.5% ± 1.0% (n = 3) in the ileum. In the large intestinal system, cinnamate 4-hydroxylase activity was detected but was too weak to be quantified. These results suggest that S. cerevisiae may afford a useful host for the development of biodrugs and may provide an innovative system for the prevention or treatment of diseases that escape classical drug action. In particular, yeasts may provide a suitable vector for biodetoxication in the digestive environment. Chemicals/CAS: cinnamate 4 monooxygenase, 9077-75-2; cinnamic acid, 4151-45-5, 538-42-1, 621-82-9; cytochrome P450, 9035-51-2; oxygenase, 9037-29-0, 9046-59-7; para coumaric acid, 7400-08-0; Cytochrome P-450 Enzyme System, 9035-51-2; Mixed Function Oxygenases, EC 1.-; Trans-Cinnamate 4-Monooxygenase, EC 1.14.13.11

Recombinant Saccharomyces cerevisiae expressing P450 in artificial digestive systems: a model for biodetoxication in the human digestive environment.

Effects of cryoprotectants on the viability and activity of freeze dried recombinant yeasts as novel oral drug delivery systems assessed by an artificial digestive system

Use of whey protein beads as a new carrier system for recombinant yeasts in human digestive tract

Living recombinant Saccharomyces cerevisiae secreting proteins or peptides as a new drug delivery system in the gut.

This invention provides compositions and methods for supplementing the detoxification systems of gastrointestinal cells to protect the body from ingested procarcinogens and other toxic substances. The compositions comprise probiotic microorganisms which have been genetically modified to express mammalian enzymes involved in detoxification of procarcinogens. The invention is practiced by feeding or otherwise administering the engineered probiotic organisms to an animal or human. The organisms colonize or otherwise become associated with the GI tract of the individual, whereupon they grow and multiply, continuing to produce the detoxifying enzymes.

Chemoprotective bacterial strains

Neonates during their first thirty days of life are particularly susceptible to pathogens because their immune system is not yet fully functional. Adults may also be unusually susceptible to pathogens when their immune system has been compromised by disease or when they have been acutely exposed to a bolus of GI pathogen. The invention provides a method of immunizing neonates and adults to pathogens by orally administering recombinant probiotic bacteria that express antibodies to the pathogens. These recombinant bacteria may be optionally administered with antibodies immunologically specific to the pathogens. The invention further provides a composition of recombinant probiotic bacteria that express antibodies to pathogen, and a method to use this composition to immunize neonates and adults.

Gastrointestinal bacterial antibody factories

La presente invention concerne des compositions et des procedes utilises pour completer l'action des systemes de detoxication des cellules gastro-intestinales, de facon a proteger l'organisme des procancerogene ingeres et d'autres substances toxiques Ces compositions renferment des micro-organismes probiotiques genetiquement modifies pour exprimer les enzymes mammiferes impliquees dans la detoxication des procancerogenes Le procede de cette invention consiste a administrer les organismes probiotiques elabores a un animal ou a un humain Ces organismes s'associent a la voie gastro-intestinale du sujet ou la colonisent, puis se developpent et se multiplient, tout en continuant a produire des enzymes de detoxication

Souches bacteriennes chimioprotectrices

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Chemoprotective bacterial strains

Gastrointestinal bacterial antibody factories

Souches bacteriennes chimioprotectrices