Antibiotics from plants

Lactic Acid B cteri. The lactic acid bacteria are ubiquitous in nature from plant surfaces to gastrointestinal tracts of many animals. These gram-positive facultative anaerobes convert carbohydrates (qv) to lactic acid and are used extensively in the food industry, for example, for the production of yogurt, cheese, sour dough bread, etc. The sour aromatic flavor imparted upon fermentation appears to be a desirable food trait. In addition, certain species produce a variety of antibiotics. 

The therapeutically active dmg can be extracted from plant or animal tissue, or be a product of fermentation (qv), as in the case of antibiotics. Frequentiy, it is synthesized and designed to correlate stmcture with therapeutic activity. Pharmacologic activity is first tested on laboratory animals. When the results ate encouraging, physical and chemical properties are determined in the so-called preformulation stage, and analytical procedures are developed for quahty control (see Qualityassurance/qualitycontrol). 

ShotweU OL, Stodola EH, Michael WR, Lindenfelser LA, Dworschack RCi Pridham TG. (1958) Antibiotics against plant disease. III. Duramycin, anew antibiotic from Streptomyces Cinnamomeus forma Azacoluta. J Am Chem Soc 80 3912-3915. 

Drags used to treat cancer are subdivided into six groups antimetabolites, alkylating agents, antibiotics, drags isolated from plants, hormones, and a group of substances not included in the classifications listed above, which are examined in another section. 

In the last few years, there has been target interest in biologically active compounds, isolated from plant species for the elimination of pathogenic microorganisms, because of the resistance that microorganisms have built against antibiotics [6] or because they are ecologically safe compounds [7]. 

Few of these have been found so far, the first not until 1944, in a poisonous South African plant, Gifblaar . The toxic principle of this was identified44 as fluoroacetic acid. A recent summary45 indicates that some 10 fluorinated natural products have now been isolated (in small amounts) largely from other plant sources, their formation being rationalized from the metabolism of fluoroacetate. The exception is nucleocidin (1), an antibiotic from a microbial source (Streptomyces calvus), originating in an Indian soil sample, and which has a ribose moiety carrying fluorine at C4. 

Effect of Rotenone and Antimycin A on Electron Transfer Rotenone, a toxic natural product from plants, strongly inhibits NADH dehydrogenase of insect and fish mitochondria. Antimycin A, a toxic antibiotic, strongly inhibits the oxidation of ubiquinol. 

N-Alkylation is an important modification of the peptide bond. In particular, N-methylation is widespread and commonly occurs in natural peptides from plants, marine sources, and various microorganisms. Several of these compounds have important biological activity, such as antibiotic (e.g., enniatins, 1 monamycins, 2 echinomycin 3 ), antitumor (e.g., bouvardin, 4 dolastatin 56 ) and immunosuppressor activity (e.g., cyclosporin 7 ). For reviews see refs 8-10. ... 

The therapeutically active drug can be extracted from plant or animal tissue, or be a product of fermentation, as in the case of antibiotics. 

Toxins and other natural products generally provide great benefit to society. For example, some of the most widely used drugs and therapeutics like streptomycin, the aminoglycoside antibiotic from soil bacteria, and acetylsalicylic acid (aspirin), the nonsteroidal anti-inflammatory from willow tree bark, are used by millions of people everyday to improve health and well-being. On the other hand, adverse encounters with toxins like fish and shellfish toxins, plant, and insect toxins do result in harm to humans. 

JD Walton. Peptide phytotoxins from plant-pathogenic fungi. In H Kleinkauf, H von Dohren, eds. Biochemistry of Peptide Antibiotics. Berlin W. de Gruyter, 1990, pp 179-203. 

Genes that code for human insulin isolated or purified from human pancreas beta cells Yeasts isolated or purified artificially from nature Microorganisms isolated or purified artificially from nature and that produce an antibiotic X Antibiotic X produced by such microorganism Human hepatocyteY Human liver tissue Z Extracts isolated from plant Y... 

In this connection, I would like to cite three examples of chemical engineering challenges in biotechnology where, while an understanding of cell behavior is needed, it is the basic chemical engineering research that will likely make the difference. One example is from plant cell culture, the second from antibiotic production, and the third from biotechnology monitoring and control. 

For control of some pest problems, materials from natural sources have proved extremely successful. In particular, many plant, human, and animal diseases are controlled by antibiotics produced by microorganisms. Insecticides from plant sources have been used effectively for many years, but the scale on which they have been used does not compare with that of the synthetic organic insecticides Introduced in the years following World War II. 

ATP-ADP translocase is specifically inhibited by very low concentrations of atractyloside (a plant glycoside) or bongkrekic acid (an antibiotic from a mold). Atractyloside binds to the translocase when its nucleotide site faces the cytosol, whereas bongkrekic acid binds when this site faces the mitochondrial matrix. Oxidative phosphorylation stops soon after either inhibitor is added, showing that ATP-ADP translocase is essential. 

Finally, it may be worthwhile to point out that one of the most successful chemotherapeutic drugs provided by nature may be considered as a non-classical active-site-directed irreversible inhibitor This drug is penicillin (70). As a non-classical antimetabolite of D-alanyl-D-alanine, it first forms a reversible complex with the enzyme peptidoglycan transpeptidase, and then by a ringopening reaction of its p-lactam moiety, it forms a covalently linked penicil-loyl-enzyme complex97. However, the reaction involves the acylation of a sulfhydryl group in the active site of the enzyme in this respect, 70 resembles the classical-type endoalkylating antimetabolites, azaserine and DON (8 and 9, see Section 2.2.). Some of the more recently discovered antibiotics and natural products from plants with antitumor activity (e.g., camptothecin) are... 

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