Assembly Line Antibiotic Synthesis

Anti-infection agents have spared countless furthermore added to the expansion in future. They are essentially delivered by the fermentation of fungi (e.g., Penicillium) and bacteria (e.g., Actinomycetes). Specifically, 80% of anti-infection agents are sourced from the family Streptomyces and uncommon actinomycetes, for example, Actinomadura, and just the 20% is created by fungal species (Lo Grasso,

Antibiotics have played an essential role in the fight against diseases and infections since the 1940’s. Antibiotics are a leading cause for the rise of global average life expectancy in the 20th and 21st century. They have greatly reduced illnesses and deaths due to diseases. With the introductions of antibiotics in the 1940’s, like penicillin into clinical practice, formally deadly illnesses became immediately curable and saved thousands of lives (Yim 2006). Antibiotic use has been beneficial and when prescribed and taken correctly their effects on patients are exceedingly valuable. However, because these drugs have been used so widely and for such a long period of time the bacteria that the antibiotics are designed to kill have adapted,

Antibiotics were introduced to people in 1929, which could restrain the normal growth of the other bacteria called antimicrobial activity, was found by British scientist Alexander Fleming by coincidence. Then scientists used antibiotics, to cure injured soldiers and got great success during the World War. With the efforts of many scientists in the past half of the century, thousand kinds of antibiotics are found, which could be natural, semi-synthetic or synthetic, and many of them are used in medical field successfully.

Tyrothricin, one of the first antibiotics discovered after penicillin, treated many wounds and helped fight diseases in the body (“Antibiotic” 1). Scientists tested the efficiency of Tyrothricin on open wounds. After twelve days, the Tyrothricin that had been administered to one of the wounds had miraculous results in comparison to the injury without the ointment (Williams 1). Tyrothricin has benefitted many people with flesh wounds particularly soldiers at war. Their accessibility to the drug had increased their bodies productivity in healing the laceration. Moreover, Actinomycete is another example of Penicillin blooming the beginning of all antibiotics. Actinomycete, when tested its capability of eliminating marine alga Phaeocystis globosa, proved to be highly efficient in that after 7 days, marine alga Phaeocystis globosa decreased its toxicity by 60% (Zhang 1). Actinomycetes contribution to society includes drugs like Bestain. When combined with Aminopeptidase, Bestain resists and reduces the size of liver cancer stem cells and also xenograft tumors (Sun 1). Derived from Penicillin, Actinomycetes is the benefactor and savior to the once ravenous diseases that once spread among people by producing many different antibiotics. Eventually, antibiotics created by cephalosporins commenced into society with drugs such as Cefixime, Cephalexin, and Cefuroxime which suppress infections like skin,

The purpose of this lab is to use genetic engineering to transform E. coli bacteria by inserting the plasmid pGLO, and to then see if the bacteria was transformed by using the antibiotic, ampicillin.

T6SS, Type VI Secretion System, is a specialized protein secretion system used by bacteria for survival. This system acts as a “gun” firing proteins into the target cell. It is one of 6 found in Gram negative bacteria and has been known to target eukaryotic cells, as well as competing bacteria. T6SS serves as a virulence factor towards its host while also effectively killing its competitors, responding in stress and horizontally transfering DNA. Certain systems also recognize other cells as themselves.

Type III secretion systems are needle like proteins that span the inner and outer membrane in gram-negative bacteria. Gram-negative bacteria with T3SS use the needle to penetrate other bacteria, and then secrete proteins from their bacterial cytoplasm into the cytoplasm of the host.

As we seen in the mechanism of action all beta-lactam antibiotics, share a basic chemical structure that includes a three carbon, one nitrogen cyclic amine structure is known as the beta-lactam ring. Beta-lactam ring attached with a side chain having a variable group to the core structure of by a peptide bond. The variation of the side chain contributes to antibacterial activity.FDA has approved over 34 beta-lactam compounds as active ingredients in drugs for human use. Beta-lactam antibiotics have the following five classes:

Polymyxin B1 (PMB1) is a small antimicrobial lipopeptide first derived from the bacterial species Bacilus Polymyxa in 1947[25, 29, 189]. It’s structure is made up of a cyclic polypeptide ring and a fatty acid tail with sequence: DabC-Thr-Leu-DPhe-Dab-DabC-Dab-Thr-Dab-OC9H17. Some of the residues forming the peptide segments are irregular amino acids such as D-Phenylalanine and α, γ-Diamino Butyric acid (DAB). DAB amino acids carry a charge of +1, and with five DABs present this gives the cationic peptide a total charge of +5 [34]. PMB1 is known to be highly potent and is selective principally to gram-ve bacteria, it is effective against all but the Proteus group [190]. It has been shown to successfully treat infections caused by Pseudomonas aeruginosa, with only limited confirmation of resistant strains developing [25, 191-193]. It has been referred to as a “last hope” antibiotic, due to it’s potency and resilience against resistance [193]. It also possesses the unconventional trait (among AMPs) of showing anti-endotoxin activity, meaning it has

Several antibiotics known to man have been already discovered since the 1940’s, in which most of it are obtained from natural sources (Chaeychomsri et al., 2010). Synthesizing large amounts of antibiotics nowadays have given way to the bacteria, as well as viruses to develop immunity to a certain antibiotic strain, thus poses a threat of bacterial resistance, as these bacterial and viral species tend to become resistant to several antibacterial agents as a result of chromosomal and genetic mutation and adaptation to the agent (Neu, 1992). Due to this setback, many scientists have also initiated solutions that could be derived from natural sources, which led to the exploration and research on several animals,

Antibiotic resistant pathogens have evolved various mechanisms to evade antibiotic action. These include preventing the antibiotic from binding or entering it, modifying the binding site of the antibiotic or producing an enzyme that deactivates the antibiotic. Therefore it has become crucial to be able to design new antimicrobial substances that can overcome these existing antibiotic- resistant pathogens. [3]

In recent years, the discovery of new broad-spectrum classes of antibiotics has slowed dramatically, partly due to an increase in rediscovery of already known antibacterial classes.11 Recently, while developing a method to eliminate the rediscovery of already known classes, Sawa et al. discovered a new broad-spectrum antibiotic they called amycolamicin (AMM) from the soil actinomycete, Amycolatopsis sp. AMM displayed powerful antibiotic activity towards many gram-positive bacteria including MRSA and some Gram-negative bacteria and is related to other potent antibiotics that all have a common

Synthetic biology has a lot to offer in fundamental research. Starting from the most well characterised laboratory organism, E.coli, we are still in half way from full knowledge of understanding the function of all its genes as the functions of 20% of them are still to be identified (Keseler et al., 2011). Moreover there are many more other microorganisms with great importance which are even less-well understood.

Antibiotics are one of the secondary metabolites produced by some fungi and bacteria that selectively inhibit the growth of another. Secondary metabolites have no role in the growth of the organisms and, indeed, may have little or no primary function within the organism. They are produced when the organism enters the stationary phase, once the initial phase of rapid growth has declined. At the stationary phase, the organisms are with the slowed growth rate, caused by depletion of nutrients, or accumulation of side products may induce their metabolic shift to the production of the secondary metabolites. In order to obtain the maximum yield of the antibiotics, it is necessary to ensure that some nutrients in the medium are limited and the organism

Significance of work: Recent advances in the fields of synthetic biology and biochemical engineering have been fundamental in progressing the ability of engineers to sustainably and quickly produce specialty chemicals in bioreactors. Using well-characterized microorganisms to generate commodity chemicals is a scalable and cost-effective method for producing a plethora of complex products that are difficult to synthesize chemically. In fact, the workhorses of biology- enzymes- enable high specificity in biochemical transformations (for example, to isomerize small molecules, or to act on a specific isomer preferentially over a different isomer) that has not yet been possible via chemistry alone. Thus, applying the synthetic biology toolbox