MB Unit 20: Antibiotic production II
36 flashcards · Other · by Yaiza Anido
What is streptomycin and by which bacteria was the initial streptomycin produced by?
Streptomycin is an antibiotic, more specifically an aminoglycoside. The initial streptomycin was produced by the bacteria streptomyces griseus.
Describe the composition of aminoglycosides
A basic core formed by a sugar and circualr alcohols. Usually 3 core subunits. The side chains then differentiate each.
Where do aminoglycosides act
Aminoglycosides act at the 30s ribosomal subunit and thus they inhibit translation by binding to it.
Mention 5 aminoglycosides
Streptomycin Neomycin Gentamycin Trobamycin Amikamycin
What is the main difference between aminoglycosides
the proportion of the sugar to the circular alcohol in the molecule
What is the core molecule in the byosinthesis of streptomycin?
The core molecule is glucose (on the contrary to penicillins for which glucose is NEVER the core molecule!!!)
What role does factor A play in streptomycin from streptomyces griseus ( a gram + bacteria)
Streptomyces griseus can form spores. The induction of the sporulation is as simple as for bacili or as for clostridium, since for streptomyces, sporulation is only possible in the pressence of factor A. It has been seen that the bacteria that produce the best yields of antibiotic production are the ones that are sporulated. Factor A is not necessarillly involved in the biosynthesis of the antibiotic, only the biology of the bacteria is conditioned by factor A. Factor A is added to the biofilm.
What is butirosin? Which m.o produce it What is the source of N and what is the C source?
a possible aminoglycoside produced by Bacillus circulans Glycerol is the source of C Soy flower is the source of N
What are macrolides.
Macrolides are a class of antibiotics derived from Saccharopolyspora erythraea (originally called Streptomyces erythreus), a type of soil-borne bacteria. Macrolides inhibit protein synthesis in bacteria by reversibly binding to the P site of the 50S unit of the ribosome preventing peptidyltransferase from adding the growing peptide attached to tRNA to the next amino acid.
How is the chemical structure of macrolides.
The chemical structure of macrolides is characterized by a macrocyclic lactonic ring and several deoxysugars bind to it. The main macrolide antibiotics have 14, 15 and 16 carbons in the laconic group: Lactonic ring with 14 atoms: Erythromycin, Roxithromycin, clarithromycin. Lactonic ring with 15 atoms: Azitromicin. Lactonic ring with 16 atoms: Espiramicin, Josamicin.
Give 2 examples of macrolides
Leucomycin and tylosine
What is thge substrate used for the production of macrolides?
The substrate used is soybean meal
Briefley explain the synthesis of the macrolide ring.
The synthesis of macrolides starts with a small compunds, usually 3C compounds such as propionate or propionyl CoA. The 3C compund then binds to methyl-malonyl-coA (has nothing to do with Propionic fermentation). This gives rise to the polyketide compound, which is linked to a multi-enzyme system (synthetase). This is then cycled. After cycling, it binds to different sugar derivatives, similar to those that make up the wall of bacteria. In this way the ring binds to the sugar derivatives giving…
What is tetracycline
Tetracycline, sold under the brand name Sumycin among others, is an oral antibiotic in the tetracyclines family of medications, used to treat a number of infections, including acne, cholera, brucellosis, plague, malaria, and syphilis.
How does tetracycline act? What m.o produces tetracycline?
Tetracyclines prevent the entry of the RNA in a ribosome. Tetracycline is mainly produced by Streptmyces spp.
Briefley explain the industrial production of tetracycline from S.Aureofaciens
In industrial production the tetracycline you start with the simplest way that guarantees a stable production and can be reproducible, and for that we use spores. The most common is sterilized grown for the spores to stay. The initial inoculum is a solid agar prepared with metal extract and glucose. Then from the bacteria we transfer to small volume enlermeyer that has a source of carbons, sugars and nitrogens and sacarose. After this initial inoculum we transfer it to a fermenter and then we a…
What is one characteristic way that polypetide antibiotics work?
Polypeptide antibiotics have ionophore properties which allows for the disruption of the membrane of some bacteria. The use of the polypeptide antibiotics is mainly for gram - bacteria in blood that have LPS which is proinflamatory.
Name some polypeptide antibiotic.
Gramicidin (linear pentadecapeptide) Polymyxin (decapeptide)
What is gramicidin and by which m.o is it produced?
Gramicidin is a linear pentadecapeptide antibiotic (polypetide antibiotic) It is produced by Bacillus brevis.
What is one characteristic of the mechanism of action of polymixins
Not only do they break the membrane but they also neutralize the toxicity of lipid A (sepsis) They are used mainly against gram (-) bacteria.
What are gramicidin A and tyrothricin? By what m.o is gramicidin A produced? What is gramicidin A mainly used for?
Gramicidin A is a mix of linear peptides. Tirotricine is a mix between gramicidin and tirocidine. It is produced by Bacillus brevis: Tirotricina (Gramicidin and Tirocidin) Both gramicidin and tyrocidine are short polypeptides which disrupt the cell membranes of some, primarily gram (+) bacteria. Tyrothricin and its component antibiotics are too toxic to be taken internally but are sometimes used as topical antibiotics Used mainly against Gram (+) bacteria that require topical treatment.
What m.o is used to synthesize the polypeptide antibiotic bacitracine?
Bacitracine: Bacilus licfheniformis
What m.o is used to synthesize gramicidine A
B.brevis
What m.o is used to synthesize nisine
streptococcus gremoris
What m.o is used to synthesize polimixine B and what does it do?
B.polymyxa It neutralizes de LPS of gram - bacteria
What m.o is used to synthesize tritricine?
B.brevis like for gramicidine A
Explain the thyotemplpate multienzymatic mechanism
The thyotemplate multienzymatic mechansim is composed of three different enzymes with different enzymatic sites. In each of the active sites fits only one amino acid and cys is the key amino acid in the active site.
Que son los antibioticos polipeptidicos?
Son peptidos cíclicos. Casi todos están sintetizados por bacterias del género Bacillus, pero hay muchos más.
What are thyotemplates?
As we know, some polypeptide antibiotics are synthesized in ribosomes but there are other polypeptides which are not. They are synthesized in a multienzymatic complex known as thyotemplates. A thyomolde consists of three different enzymatic site, and in each active site only one aa fits. The key amino acid is cystine
Explain the relationship between cystine and the thyomolde.
cCustine is the aa iwth the SH group and thus is the kkey amino acid in teh catalicitc site of the synthesis. Cysteine is always located in a specific position within a reactive site of the enzyme and a unique site for the binding of a particular amino acid. Each amino acid binds at a different active centre.
Cycloserine
initially produced by Streptomyces orchidaceus. Cell wall inhibition.
Vancomycin
acted on the synthesis and secretion of the bricks that make the cell wall. It is not affected by the beta-lactams, so it could be an alternative when you have MRSA. In addition, most of the people who are allergic to antibiotics are allergic to beta-lactams. Produced by S. orientalis.
Ansamycins
very hard to synthesize them chemically. Produced by Amycolaptosis mediterrani, and it is very interesting because it could be used as a second line antibiotic when the first line does not work. It works on intracellular bacteria, which is interesting because there are many antibiotics that cannot do that.
Novobiomycin. What does it target and by what is it produced?
Novobiocin targets the DNA topoisomerase II Produced by S.niveus
Actinomycin D
Antibiotic that doesn’t target bacteria but rapid tumors. Created by Streptomyces parvulus. Since then many other antibiotics have been used in the treatment of tumors, which most act on a DNA level, by binding to the mayor or minor groove and ralentizizing the polymerase; and some of them affecting topoisomerases to indice DNA breaks.
What are ganciclovir and acyclovir?
These are nucleoside and nucleotide analogues produced by m.o which can be converted by the enzyme thymidin kinase, pressent in all herpes viruses. The enzyme will convert them into analogues that can not be used which stops the DNA synthesis and the replication of the m.o