• 한국미생물·생명공학회지
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• 제23권6호
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• pp.647-651
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• 1995

A tylosin-hyperproductive mutant of S. fradiae MNU20 was isolated among 3500 strains obtaincd from either MNNG- or UV-treated Streptomyces fradiae NRRL2702. The composition of optimal medium for tylosin production was formulated as followed as: 4 g soluble starch, 1 g glucose, 1 g corn steep liquor, 7.5 ml soy bean oil, 0.2 g KH$_{2}$PO$_{4}$, 1 g Na$_{2}$S$_{2}$O$_{3}$$\cdot $5H$_{2}$O, 2 g CaCO$_{3}$, 2 g NaCl, 0.001 g CoCl$_{2}$$\cdot $6H$_{2}$O in 1 liter of distilled water. With the optimal medium, S. fradiae MNU20 was able to produce 159 mg tylosin (g biomass)$^{-1}$, indicating that tylosin productivity of Streptomyces fradiae NRRL2702 was increased 14 times higher by mutation. When the effect of valine, succinate, and natural zeolite on tylosin production was investigated by using the optimal medium, these substances essentially enhanced tylosin production and their addition time during culture period appeared to be critical for the increase of tylosin production.

• 미생물학회지
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• 제25권3호
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• pp.189-197
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• 1987

배지성분으로 첨가된 glutamate의 농도가 균의성장고 tylosin 생합성에 미치는 영향을 조사하였다. 그 결과 oxaloacetate를 공동기질로 사용하는 효소의 활성에 의하여 균의 성장과 tylosin의 생합성이 조절됨을 알았다. 즉, citrate synthase와 aspartate aminotransferase의 활성은 균의 성장에 아주 긴요하며 methylmalonyl-CoA carboxytransferase의 활성은 tylosin 생합성에 아주 중요한 효소임을 알았다. Glutamate의 농도는 우의 효소의 활성에 직접적으로 영향을 주고 있음을 알았다.

• 미생물학회지
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• 제25권4호
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• pp.353-359
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• 1987

균 성장속도가 tylosin 생합성에 미치는 영향을 조사하기 위하여, 여러 성장속도로 배양한 균체내에서 oxaloacetate 대사에 관여하는 효소들의 활성을 살펴보았다. 그 결과, 비 tylosin 생합성 속도($q_{p}$ )는 성장속도 $0.013h^{-1}$까지는 성장속도와 함께 증가하지만, 더 높은 성장속도에선 감소됨을 알 수 있었다. Citrate synthase, aspartate aminotransferase와 PEP carboxylase의 활성 및 합성은 $0.013h^{-1}$ 보다 낮은 성장속도에선 매우 낮게 나타났으며, 반면 methylmaionyl-CoA carboxyltransferase의 활성 및 합성은 tylosin 생합성과 마찬가지로 높은 성장속도에선 감소되었다. 따라서 tylosin 생합성은 균 성장속도에 의해 조절됨을 명백히 알 수 있었다.

• 대한수의학회지
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• 제35권1호
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• pp.131-135
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• 1995

This study was performed to develop immnoassay method of detecting the residual tylosin and to investigate the residues using HPLC(high performance liquid chromatography) in animal products. Obtained results are the followings: 1. To develop immunoassay method, the conjugation of activated tylosin tartarate ester derivatives and BSA (bovine serum albumin) was certified at the 290nm of maximal absorbance which tylosin tartrate have. 2. The titration of anti-serum produced from rabbit immunized with the conjugator as an immunogen was too low to analyze the tylosin. 3. The residual tylosin can be detected by 0.2 ppm using HPLC. 4. Recovery of tylosin from spiked pork samples measured using HPLC was $87.4{\pm}4.0%$. 5. When the levels of tylosin residues in swine liver and kindney were measured on HPLC. The level was over the maximum tolerance level in one out of ten samples of each organ.

• Journal of Microbiology and Biotechnology
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• 제17권7호
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• pp.1071-1078
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• 2007

Using a 50-1 airlift bioreactor, for the effective production of tylosin from Streptomyces fradiae TM-224 using raw cornmeal as the energy source, various environmental factors were studied in flask cultures. The maximum tylosin concentration was obtained at $32^{\circ}C$ and pH between 7.0 and 7.5. When seed was inoculated after 24 h of culture, the maximum tylosin concentration, 5.7 g/l, was obtained after 4 days of culture. Various concentrations of raw cornmeal were tested to investigate the optimum initial concentration for the tylosin production. An initial raw cornmeal concentration of 80 g/l gave the highest tylosin concentration, 5.8 g/l, after 5 days of culture. Of the various nitrogen sources, soybean meal and fish meal were found to be the most effective for the production of tylosin. In particular, with the optimal mixing ratio, 12 g/l of soybean meal to 14 g/l of fish meal, 7.2 g/l of tylosin was obtained after 5 days of culture. To compare raw cornmeal and glucose for the production of tylosin in the 50-1 airlift bioreactor for 10 days, fed-batch cultures were carried out under the optimum culture conditions. When raw com meal was used as the energy source, the tylosin production increased with increasing culture time. The maximum tylosin concentration after 10 days of culture was 13.5 g/l, with a product yield from raw cornmeal of 0.123 g/g of consumed carbon source, which was about 7.2 times higher than that obtained when glucose was used as the carbon source.

• Journal of Microbiology and Biotechnology
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• 제26권5호
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• pp.876-882
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• 2016

Tylosin has been used as a livestock feed additive and antibiotic growth promoter for many years. However, the mode of action by which tylosin enhances animal growth is unclear. We used high-throughput sequencing of 16S rRNA genes to investigate the effects of tylosin as a feed additive on swine gut microbiota. No significant difference in the rate of weight increase was observed between control and tylosin-treated pigs during a 10-week feeding trial. However, tylosin-treated pigs showed rapid increases in the relative abundance of the phylum Firmicutes. Increases in Firmicutes species are associated with (so-called) obese-type gut microbiota. The abundance of species of four families of the phylum Firmicutes (Streptococcaceae, Peptococcaceae, Peptostreptococcaceae, and Clostridiaceae) correlated positively with host weight gain. The abundance of Streptococcaceae family bacteria was least affected by tylosin treatment. Distribution analysis of operational taxonomic units (OTUs) showed that both control and tylosin-treated pigs exhibited similar OTU alterations during growth. However, the tylosin-treated group showed distinctive alterations in gut microbiota when the host weighed approximately 60 kg, whereas similar alterations occurred at around 80 kg in the control group. Our results suggest that use of tylosin accelerates maturation of swine gut microbiota rather than altering its composition.

• 대한수의학회지
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• 제41권1호
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• pp.13-19
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• 2001

A simple and rapid analytical method for the determination of tylosin in chicken, pork and muscle was established by High-Performance Liquid Chromatography(HPLC). Chicken, pork and beef muscle(5 g) were fortified by adding the $0.2{\mu}g/ml$ of standard tylosin and the drug was extracted from meats with 70% acetonitrile(ACN) and followed by liquid-liquid partition for clean-up procedure. Then $20{\mu}l$ portion of ACN elution was directly analyzed by HPLC with spectra 100 variable wavelength detector, and unfortified blank control were treated similarly. The average recovery rate of tylosin added to chicken, pork and beef muscle were $83{\pm}2.3$, $96{\pm}3.3$ and $92{\pm}1.6$(%) at the level 0.2 ppm, respectively. No tylosin residues in marketing meats. These results suggested that HPLC methodology could be acceptable for the extraction, determination and screening of tylosin residues in edible meats.

• Journal of Microbiology and Biotechnology
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• 제33권6호
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• pp.831-839
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• 2023

Tylosin is a potent veterinary macrolide antibiotic produced by the fermentation of Streptomyces fradiae; however, it is necessary to modify S. fradiae strains to improve tylosin production. In this study, we established a high-throughput, 24-well plate screening method for identifying S. fradiae strains that produce increased yields of tylosin. Additionally, we constructed mutant libraries of S. fradiae via ultraviolet (UV) irradiation and/or sodium nitrite mutagenesis. A primary screening of the libraries in 24-well plates and UV spectrophotometry identified S. fradiae mutants producing increased yields of tylosin. Mutants with tylosin yield 10% higher than the wild-type strain were inoculated into shake flasks, and the tylosin concentrations produced were determined by high-performance liquid chromatography (HPLC). Joint (UV irradiation and sodium nitrite) mutagenesis resulted in higher yields of mutants with enhanced tylosin production. Finally, 10 mutants showing higher tylosin yield were re-screened in shake flasks. The yield of tylosin A by strains UN-C183 (6767.64 ± 82.43 ㎍/ml) and UN-C137 (6889.72 ± 70.25 ㎍/ml) was significantly higher than that of the wild-type strain (6617.99 ± 22.67 ㎍/ml). These mutant strains will form the basis for further strain breeding in tylosin production.

• Journal of Microbiology and Biotechnology
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• 제18권9호
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• pp.1485-1491
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• 2008

Tylosin biosynthesis is controlled in cascade fashion by multiple transcriptional regulators, acting positively or negatively, in conjunction with a signalling ligand that acts as a classical inducer. The roles of regulatory gene products have been characterized by a combination of gene expression analysis and fermentation studies, using engineered strains of S. fradiae in which specific genes were inactivated or overexpressed. Among various novel features of the regulatory model, involvement of the signalling ligand is not essential for tylosin biosynthesis.

• Journal of Veterinary Science
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• 제21권3호
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• pp.35.1-35.11
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• 2020

Background: Despite common use of tylosin in turkeys, the pharmacokinetic (PK) data for this drug in turkeys is limited. Within a few months of growth, PK of drugs in turkeys undergoes changes that may decrease their efficacy due to variable internal exposure. Objectives: The objective of this study was to investigate the influence of age on the PK of a single intravenous (i.v.) and oral administration of tylosin to turkeys at a dose of 10 and 50 mg/kg, respectively. Methods: Plasma drug concentrations were measured using high-performance liquid chromatography with UV detection. The PK parameters were assessed by means of non-compartmental approach and were subjected to allometric analysis. Results: During a 2.5-month-long period of growth from 1.4 to 14.7 kg, the median value for area under the concentration-time curve after i.v. administration increased from 2.61 to 7.15 mg × h/L and the body clearance decreased from a median of 3.81 to 1.42 L/h/kg. Over the same time, the median elimination half-life increased from 1.03 to 2.96 h. For the oral administration a similar trend was noted but the differences were less pronounced. Bioavailability was variable (5.76%-21.59%) and age-independent. For both routes, the plasma concentration of the major tylosin metabolite, tylosin D, was minimal. Protein binding was age-independent and did not exceed 50%. Allometric analysis indicated a relatively poor predictivity of clearance, volume of distribution and elimination half-life for tylosin in turkeys. Conclusions: Age has a significant impact on tylosin PK in turkeys and dosage adjustment may be needed, particularly in young individuals.