Estimation of the kinetic constants and elucidation of trends in growth and erythromycin production in batch and continuous cultures of Saccharopolyspora erythraea using curve-fitting techniques

A miniature electrode was used to measure, for the first time, the timedependent change in dissolved oxygen concentration of small-scale cultures of two actinomycete species at various aeration efficiencies in both complex and defined media. Erythromycin was produced in both oxygen-limited and oxygen-sufficient conditions in shaken flask and inclined tube cultures of Saccharopolyspora erythraea and a further, novel, secondary metabolite was produced only under oxygen limitation. In contrast, vancomycin was only produced in oxygen-suff icient cultures of Amycolatopsis orientalis. Similar results were obtained in batch bioreactor cultures. These findings indicate that oxygen limitation acts in an analogous manner to substrate limitation imposed by dissolved nutrients, stimulating secondary metabolite production in some cases and inhibiting it in others. The implications of these findings in screening programmes for novel secondary metabolites are discussed.

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“…evtbraea cultures (Fig. 2a), following similar kinetics to those observed by us previously (McDermott et al, 1993). Antibiotic production in Amy.…”

Section: Antibiotic Production In Glucose-limited Culturesupporting

confidence: 72%

“…Specific growth rates were calculated using the partial cubic spline interpolation methodology described by us previously (Bushel1 et al, 1993;McDermott et al, 1993). The idea of using cubic spline interpolation of fermentation data was first proposed by Oner et a/.…”

Section: Anti Biotic Assaysmentioning

confidence: 99%

Oxygen limitation can induce microbial secondary metabolite formation: investigations with miniature electrodes in shaker and bioreactor culture

Clark

Bushell

1995

Microbiology

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“…(Potvin and Péringer, 1994a, b;Bushell et al, 1997b;Clark et al, 1995;McDermott et al, 1993). For example, the use of ammonium sulfate (Potvin and Péringer, 1994a, b), chemostat cultivation under phosphate limitation (Trilli et al, 1987) and batch culture under N (nitrate) limitation (McDermott et al, 1993;Bushell et al, 1997b) has been reported to result in growth-associated erythromycin production. Various explanations have been given for this phenomenon: Potvin and Peringer (1994b) maintain that erythromycin production by S. erythraea under nutrient-rich conditions can be induced by local diffusional limitations imposed by early formation of mycelia pellets; on the other hand, Bushell et al (1997b) claim that growth-associated erythromycin production can occur with growth substrates for which S. erythraea has low affinity.…”

Section: Resultsmentioning

confidence: 99%

“…In the case of erythromycin production by S. erythraea, previous research has shown that, depending on the environment of S. erythraea cultivation, erythromycin production can be both growth and non-growth associated. (Potvin and Péringer, 1994a, b;Bushell et al, 1997b;Clark et al, 1995;McDermott et al, 1993). For example, the use of ammonium sulfate (Potvin and Péringer, 1994a, b), chemostat cultivation under phosphate limitation (Trilli et al, 1987) and batch culture under N (nitrate) limitation (McDermott et al, 1993;Bushell et al, 1997b) has been reported to result in growth-associated erythromycin production.…”

Section: Resultsmentioning

confidence: 99%

The inter-relationship between inoculum concentration, morphology, rheology and erythromycin productivity in submerged cultivation of Saccharopolyspora erythraea

Ghojavand

Bonakdarpour

Heydarian

et al. 2011

Braz. J. Chem. Eng.

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-Submerged cultivation of Saccharopolyspora erythraea, at different initial spore concentrations, was carried out to study the inter-relationship between inoculum concentration, morphology, rheology and erythromycin production. Pellet morphology was dominant in runs at 10 3 and 10 4 spore/ml initial spore concentrations, whereas there was a significant presence of clump morphology in runs at initial spore concentrations of 10 5 -10 7 spore/ml. The S. erythraea cultivation broths exhibited Newtonian rheology in runs at initial spore concentrations of 10 3 and 10 4 spore/ml, whereas at higher initial spore concentrations the rheological data could be fitted with the power law model. Runs in which clump morphology was predominant resulted in the highest erythromycin productivities. The findings of the present work suggest that the predominance of clump morphology, smaller sized clumps and, in the case of non-Newtonian S. erythraea cultivation broths, a decrease in viscosity enhance erythromycin production.

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“…To decipher the mechanisms whereby Streptomyces bacteria sense changes in their environment and transduce them into expression of specific secondary metabolic gene sets, it is essential to clearly define the environmental conditions which trigger antibiotic production. The dynamic behavior of batch cultures (23) hinders this effort.…”

mentioning

confidence: 99%

Environmental signals triggering methylenomycin production by Streptomyces coelicolor A3(2)

et al. 1997

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Methylenomycin production by Streptomyces coelicolor A3(2) may be triggered by either of two environmental signals: alanine growth-rate-limiting conditions and/or an acidic pH shock. The production of this SCP1-encoded antibiotic was studied by using batch and chemostat cultures. Batch cultures indicated a role for both nutritional status and culture pH in its regulation. Steady-state methylenomycin production and transcription of an mmy gene under alanine but not glucose growth-rate-limiting conditions was demonstrated in chemostat culture. Transient mmy expression and methylenomycin production occurred following an acidic pH shock. This stimulation of methylenomycin production occurred independently of the nutritional status of the growth environment. Antibiotic production was partially suppressed under alanine compared with glucose growthrate-limiting conditions following the acidic pH shock. A low specific growth rate was a prerequisite for both steady-state and transient production of methylenomycin.The traditional view of antibiotic production in Streptomyces bacteria is that it is restricted to the stationary phase (idiophase) of the batch growth cycle and is triggered by environmental factors which give rise to this state (reviewed in reference 2). This view has arisen from the extensive use of batch culture in academic studies and industrial processes. To decipher the mechanisms whereby Streptomyces bacteria sense changes in their environment and transduce them into expression of specific secondary metabolic gene sets, it is essential to clearly define the environmental conditions which trigger antibiotic production. The dynamic behavior of batch cultures (23) hinders this effort.A number of authors (1,8,10,16,18,21,24,28,31,32) have studied antibiotic production by streptomycetes by using chemostat culture. From these studies, it is clear that secondary metabolism is not strictly associated with zero growth (22) and that antibiotic production is subject to a growth rate dependence. Also, in a number of cases, antibiotic production has been demonstrated to be influenced by the nutritional status of the growth environment and hence is dependent on a type of catabolite repression or metabolite interference (2). However, in many cases, researchers have reported the presence of metabolite interference based solely on studies using batch culture.The antibiotic methylenomycin is one of at least five secondary metabolites synthesized by Streptomyces coelicolor A3(2) (33). Its biosynthetic genes (mmy), together with a resistance determinant (mmr), are all carried on a large, linear plasmid, SCP1 (17). In a previous report (12), we described a set of nutritional conditions which permitted the biosynthesis of methylenomycin in batch culture. Methylenomycin was produced toward the end of the active growth phase but prior to the complete consumption of the growth stoichiometrically limiting substrate, alanine. In these experiments, the pH was not controlled and decreased during the growth phase from 7.2 to 5.5. Low...

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Estimation of the kinetic constants and elucidation of trends in growth and erythromycin production in batch and continuous cultures of Saccharopolyspora erythraea using curve-fitting techniques

Cited by 26 publications

References 12 publications

Oxygen limitation can induce microbial secondary metabolite formation: investigations with miniature electrodes in shaker and bioreactor culture

Oxygen limitation can induce microbial secondary metabolite formation: investigations with miniature electrodes in shaker and bioreactor culture

The inter-relationship between inoculum concentration, morphology, rheology and erythromycin productivity in submerged cultivation of Saccharopolyspora erythraea

Environmental signals triggering methylenomycin production by Streptomyces coelicolor A3(2)

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