Biotechnological Production of Statins: Metabolic Aspects and Genetic Approaches

2019 ◽  
Vol 20 (15) ◽  
pp. 1244-1259
Author(s):  
Roberval N.M. Neto ◽  
Edelvio de Barros Gomes ◽  
Lucas Weba-Soares ◽  
Léo R.L. Dias ◽  
Luís C.N. da Silva ◽  
...  

Statins are drugs used for people with abnormal lipid levels (hyperlipidemia) and are among the best-selling medications in the United States. Thus, the aspects related to the production of these drugs are of extreme importance for the pharmaceutical industry. Herein, we provide a non-exhaustive review of fungal species used to produce statin and highlighted the major factors affecting the efficacy of this process. The current biotechnological approaches and the advances of a metabolic engineer to improve statins production are also emphasized. The biotechnological production of the main statins (lovastatin, pravastatin and simvastatin) uses different species of filamentous fungi, for example Aspergillus terreus. The statins production is influenced by different types of nutrients available in the medium such as the carbon and nitrogen sources, and several researches have focused their efforts to find the optimal cultivation conditions. Enzymes belonging to Lov class, play essential roles in statin production and have been targeted to genetic manipulations in order to improve the efficiency for Lovastatin and Simvastatin production. For instance, Escherichia coli strains expressing the LovD have been successfully used for lovastatin production. Other examples include the use of iRNA targeting LovF of A. terreus. Therefore, fungi are important allies in the fight against hyperlipidemias. Although many studies have been conducted, investigations on bioprocess optimization (using both native or genetic- modified strains) still necessary.

2013 ◽  
Vol 5 (2) ◽  
pp. 313-317 ◽  
Author(s):  
Saraswati Bisht

Assessment of different sources of carbon and nitrogen in terms of dry weight biomass of four selected aquatic hyphomycetes viz; Flagellospora penicilloides Ingold, Pestalotiopsis submersus Sati and Tiwari, Tetrachaetum elegans Ingold and Tetracladium marchalianum De Wildeman was made for their nutritional requirements. Eight carbon sources and ten nitrogen sources were singly added to the basal media in order to provide 4g of carbon and 1g of nitrogen per litre of distilled water. Among carbon compounds glucose and sucrose were found to be most suitable sources of carbon for all the four fungal isolates, where as fructose proved good for T. marchalianum, P. submersus and F.penicilloides fairly. Cellulose was found a poor source of carbon for the growth of all these isolates. The inorganic sources of nitrogen were found as good nitrogen sources with preference for ammonium ions. Suitability of amino acids was found variable from species to species for nitrogen. T.elegans and T.marchalianum had their maximum growth in asparagines, whereas, P. submersus had their highest growth in proline. Cysteine was observed as a good source of nitrogen for almost all the fungal isolates used. Anova calculated for these observed data showed significant variations in the dry weight production of different fungal species grown in different sources of carbon and nitrogen(P<0.01).


Author(s):  
Lucyna Kornecki ◽  
E. M. Ekanayake

The descriptive part of this research focuses on the latest trends in U.S. inward Foreign Direct Investment (FDI) and describes the U.S. inward FDI flows and stock as a percentage of Gross Domestic Product (GDP) and includes geographic and sectoral distribution of inward U.S. FDI. The important part of U.S. inward FDI profile relates to inward U.S. FDI employment and inward U.S. FDI financial flows, which include equity, reinvested earnings, and intercompany debt. The corporate players, Mergers and Acquisitions(M&A’s) and green field investment are discussed briefly. The empirical part of this research investigates state-based factors affecting the inward FDI employment among 50 states of the United States and is based on data collected by the Commerce Department’s Bureau of Economic Analysis (BEA). This study identifies several state-specific determinants of FDI employment. The results indicate that the major factors exerting positive impact on inward U.S. FDI employment are: real wages, infrastructure, unionization level, educational attainment, FDI stock, and manufacturing density. In addition, the results show that gross state product growth rate, real per capita taxes has negative impact on FDI employment.


1981 ◽  
Vol 27 (7) ◽  
pp. 685-691 ◽  
Author(s):  
E. A. Barnett ◽  
W. A. Ayers

Three of five isolates of Sporidesmium sclerotivorum, a mycoparasite of Sclerotinia spp., grew well on an agar medium containing mineral salts, glucose, thiamine, and glutamine or Casamino acids as the nitrogen source. The nitrogen requirement for two of the isolates was satisfied by NH4Cl, Casamino acids, or glutamine. Glutamine was the best single nitrogen source. Only one isolate, CS-1, was used in further nutritional studies. The optimum concentration of glutamine for growth was 5 g/L. Glucose, mannose, mannitol, and cellobiose were excellent carbon sources. A glucose concentration of 20 g/L was optimum. Mannitol supported greater growth than glucose with Casamino acids as the nitrogen source but glucose was the superior carbon source with glutamine as the nitrogen source. Greatest growth was achieved with a combination of these carbon and nitrogen sources. Sporidesmium sclerotivorum, isolate CS-1, required thiamine for growth and sporulation. Biotin stimulated growth. The fungus developed maximally within the range of pH 5.0–5.5 and growth was greatly reduced at a pH below 4.0 or above 6.0. Control of acidity by the periodic addition of NaOH solution permitted substantially increased growth. The optimum temperature for growth was 22.5–25.0 °C but production of macroconidia was greatest at 15–20 °C.


2010 ◽  
Vol 65 (7-8) ◽  
pp. 528-531 ◽  
Author(s):  
Alapati Kavitha ◽  
Muvva Vijayalakshmi

Cultural factors affecting the production of L-asparaginase by Streptomyces tendae isolated from laterite soil samples of Guntur region were investigated on glycerolasparagine- salts (modified ISP-5) broth. Optimal yields of L-asparaginase were recorded in the culture medium with the initial pH 7.0 incubated at 30 °C for 72 h. The strain utilized sucrose (2%) and yeast (2%) extract as carbon and nitrogen sources for L-asparaginase production. The productivity of L-asparaginase was slightly enhanced when the strain was treated with cell-disrupting agents like EDTA. The crude enzyme was purifi ed to homogeneity by ammonium sulfate precipitation, Sephadex G-100 and CM-Sephadex G-50 gel filtration. By employing sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the molecular weight of the enzyme was recorded as 97.4 kDa. This is the first report on production and purification of L-asparaginase from S. tendae.


2015 ◽  
Vol 58 (1) ◽  
pp. 23-29
Author(s):  
Memuna Ghafoor Shahid ◽  
Muhammad Nadeem

The present study deals with the screening of fungal species and suitable fermentation medium for the production of ergot alkaloids. Various species of genus Penicillium were grown on differentfermentation media by employing surface culture fermentation technique to achieve the most suitable medium and the best Penicillium sp. The results showed that medium M5 gave maximum yield withPenicillium commune. Different culture conditions such as effect of different carbon and nitrogen sources, their concentration levels, different pH values and sizes of inoculum on the production of ergot alkaloids were also studied to improve the yield. Maximum production of ergot alkaloids (4.32 mg/L) was achieved with 15 mL spore suspension at pH 5 in fermentation medium containing 35% (w/v) sucrose. All these  results indicate that culture conditions are very much crucial to improve the yield of ergot alkaloids produced by Penicillium commune through surface culture process. 


HortScience ◽  
2009 ◽  
Vol 44 (6) ◽  
pp. 1757-1761 ◽  
Author(s):  
John B. Stiglbauer ◽  
Haibo Liu ◽  
Lambert B. McCarty ◽  
Dara M. Park ◽  
Joe E. Toler ◽  
...  

‘Diamond’ zoysiagrass [Zoysia matrella (L.) Merr.] has a potential to become a new alternative warm-season putting green turfgrass. The main objective of the study was to determine factors affecting establishment speed for ‘Diamond’ zoysiagrass as a putting green in the southern transition zone of the United States. Two sprigging rates, three nitrogen (N) sources, two N rates, and two mowing heights (2.5 and 3.2 mm) were compared at Clemson University, Clemson, SC. Sprigs of ‘Diamond’ zoysiagrass were planted at rates of 91 or 182 m3·ha−1 in 2007 and repeated in 2008. Urea, ammonium nitrate, and ammonium sulfate were applied at 1.7 or 3.4 g N/m2/week from weeks after sprigging (WAS) 3 to 10. Rates were halved from WAS 11 to 16. The N fertilizers were applied as solutions weekly for 16 weeks. Weekly percent cover, turf color ratings, root and clipping sample, and ball rolling were collected for both years. A significant difference occurred in turf cover between high and low sprig rates. Turf color and cover results show that high rates of fertility associated with high rates of sprigs produced 100% turf cover at WAS 11 and 13 in both years. At the 2.5-mm mowing height, ball rolling reached 258 cm in August and was significantly faster than the 3.2-mm mowing height. Results show ‘Diamond’ zoysiagrass can be established within the same growing season to meet a playable putting green quality, but the establishment speed may vary depending on summer monthly temperature fluctuations.


1994 ◽  
Vol 72 (2) ◽  
pp. 198-202 ◽  
Author(s):  
M. Shankar ◽  
D. I. Kurtböke ◽  
K. Sivasithamparam

Growth and antifungal activity of a sterile red fungus against Gaeumannomyces graminis var. tritici (the take-all fungus) in vitro was greatly influenced by nutritional and environmental conditions. The utilization by the sterile red fungus of various carbon and nitrogen sources differed considerably at pH 5.5 and 6.5. Maximum growth of the sterile red fungus occurred when pectin was supplied as the carbon source at both pH levels. As nitrogen sources, NH4H2PO4 supported maximum growth at pH 5.5, whereas Ca(NO3)2 was the best at pH 6.5. Pectin strongly enhanced the antifungal activity of the sterile red fungus towards the take-all fungus as did Ca(NO3)2 supplied as a N source. There was, however, little or no antagonism in the presence of calcium citrate, arabinose, leucine, or arginine. In general, antagonism was optimal at 20 °C and at pH 5.5. Key words: sterile red fungus, Gaeumannomyces graminis var. tritici, biological control.


Author(s):  
Lucyna Kornecki ◽  
E. M. Ekanayake

The descriptive part of this research focuses on the latest trends in US inward Foreign Direct Investment (FDI) and describes the US inward FDI flows and stock as a percentage of Gross Domestic Product (GDP) and includes geographic and sectoral distribution of inward US FDI. The important part of US inward FDI profile relates to inward US FDI employment and inward US FDI financial flows, which include equity, reinvested earnings, and intercompany debt. The corporate players, Mergers and Acquisitions(M&A's) and green field investment are discussed briefly. The empirical part of this research investigates state-based factors affecting the inward FDI employment among 50 states of the United States and is based on data collected by the Commerce Department's Bureau of Economic Analysis (BEA). This study identifies several state-specific determinants of FDI employment. The results indicate that the major factors exerting positive impact on inward US FDI employment are: real wages, infrastructure, unionization level, educational attainment, FDI stock, and manufacturing density. In addition, the results show that gross state product growth rate, real per capita taxes has negative impact on FDI employment.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
K. Rinu ◽  
Mukesh Kumar Malviya ◽  
Priyanka Sati ◽  
S. C. Tiwari ◽  
Anita Pandey

Three species of Aspergillus, namely, A. niger, A. glaucus and A. sydowii, isolated from soil samples collected from the Indian Himalayan Region (IHR), have been investigated for solubilization of aluminium phosphate and iron phosphate in the presence of different carbon and nitrogen sources. Preference of each fungal species varied for nitrogen and carbon sources, in terms of phosphate-solubilization. Among three species, Aspergillus niger gave the best results; it solubilized 32% and 8% of the supplemented aluminium phosphate and iron phosphate, respectively. The results indicated that the effect of carbon and nitrogen sources can influence the phosphate solubilizing efficiency of all the three Aspergillus spp. tested. All the three species were found to be plant-growth promoters in bioassays conducted under greenhouse conditions. The Al and Fe phosphate solubilization efficiency, investigated in the present study, is at the lower end of their previously reported tricalcium phosphate solubilization efficiency. The cultures are likely to have better field applications in agrobiotechnology, due to their potential towards solubilization of Al and Fe phosphates, which are known to have lower solubility through microbial activity.


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