• Microbiology and Biotechnology Letters
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• v.23 no.6
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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.

• Korean Journal of Microbiology
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• v.25 no.3
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• pp.189-197
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• 1987

The aim of the present study was to investigate the effect of glutamate on the biosynthesis of tylosin. Activities of enzymes involved in the metabolic pathway of glutamate to form tylactone, an essential precursor of tylosin, were determined using Streptomyces fradiae grown at different concentration of glutamate. As results, it was found that cell growth and tylactone formation was controlled by the metabolic flux of oxaloacetate. It was clear that cell growth was favored by the activities of citrate synthase and aspartate aminotransferase, while the tylactone synthesis was stimulated by the activity of methylmalonyl-CoA carboxyltransferase. Therefore it was concluded that channelling of oxaloacetate was a point for favoring either cell growth or tylosin biosynthesis.

• Korean Journal of Microbiology
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• v.25 no.4
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• pp.353-359
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• 1987

The aim of the present study was to investigate the effects of growth rate on the biosynthesis of tylosin in Streptomyces fradiae. In order to elucidate the relation between the growth rate and the tylosin formation rate, the activities of enzymes involved in oxaloacetate metabolism were determined using cells grown at different growth rates in chemostats. As the results, it was found that the specific rate of tylosin formation($q_{p}$) was closely related to the specific cell growth rate and the maximum value of $q_{p}$ was 1.1mg tylosin, $q_{p}$ cell, $0.013h^{-1}$ at the growth rate $0.013h^{-1}$. However further increase in the growth rate over $0.013h^{-1}$ resulted in apparent decrease of $1_{p}$. The synthesis and activities of citrate synthase, aspartate aminotransferase, and PEP carboxylase were very low at lower growth rate. On the other hand, the activity and synthesis of methylmalonyl-CoA carboxyltransferase was closely related to tylosin formation. Therefore it was concluded that tylosin formation was apparently controlled by the growth rate.

• Korean Journal of Veterinary Research
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• v.35 no.1
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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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• v.17 no.7
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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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• v.26 no.5
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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.

• Korean Journal of Veterinary Research
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• v.41 no.1
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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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• v.33 no.6
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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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• v.18 no.9
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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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• v.21 no.3
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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.