The dynamic regulation of nitrogen and phosphorus in the early phase of fermentation improves the erythromycin production by recombinant Saccharopolyspora erythraea strain

Zhang, Qiang; Chen, Yong; Hong, Ming; Gao, Yang; Chu, Ju; Zhuang, Yingping; Zhang, Siliang

doi:10.1186/s40643-014-0015-7

Cited by 9 publications

(4 citation statements)

References 20 publications

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“…The overexpression of icd is expected to enhance the intracellular 2‐oxoglutarate pool generated from isocitrate. 2‐oxoglutarate plays a role of indicating the cellular nitrogen status, and the anticipated larger 2‐oxoglutarate pool in E3::icd relative to E3 signaled nitrogen deficiency that would lead to a stimulated nitrogen metabolism (Radchenko et al, 2013), which exerts negative effects on the biosynthesis of erythromycin (Liao et al, 2015; Zhang et al, 2014). However, the overexpression of sucBA could avoid the accumulation of 2‐oxoglutarate.…”

Section: Resultsmentioning

confidence: 99%

Comparative genomic and transcriptomic analysis guides to further enhance the biosynthesis of erythromycin by an overproducer

Qiao

et al. 2022

Biotech & Bioengineering

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Omics approaches have been applied to understand the boosted productivity of natural products by industrial high-producing microorganisms. Here, with the updated genome sequence and transcriptomic profiles derived from highthroughput sequencing, we exploited comparative omics analysis to further enhance the biosynthesis of erythromycin in an industrial overproducer, Saccharopolyspora erythraea HL3168 E3. By comparing the genome of E3 with the wild type NRRL23338, we identified fragment deletions inside 56 coding sequences and 255 single-nucleotide polymorphisms over the genome of E3. A substantial number of genomic variations were observed in genes responsible for pathways which were interconnected to the biosynthesis of erythromycin by supplying precursors/ cofactors or by signal transduction. Furthermore, the transcriptomic data suggested that genes involved in the biosynthesis of erythromycin were significantly upregulated constantly, whereas some genes in biosynthesis clusters of other secondary metabolites contained nonsense mutations and were expressed at extremely low levels. Through comparative transcriptomic analysis, L-glutamine/ L-glutamate and 2-oxoglutarate were identified as reporter metabolites. Around the node of 2-oxoglutarate, genomic mutations were also observed. Based on the omics association analysis, readily available strategies were proposed to engineer E3 by simultaneously overexpressing sucB (coding for 2-oxoglutarate dehydrogenase E2 component) and sucA (coding for 2-oxoglutarate dehydrogenase E1 component), which increased the erythromycin titer by 71% compared to E3 in batch culture. This study provides more promising molecular targets to engineer for enhanced production of erythromycin by the overproducer.

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Section: Resultsmentioning

confidence: 99%

Comparative genomic and transcriptomic analysis guides to further enhance the biosynthesis of erythromycin by an overproducer

Qiao

et al. 2022

Biotech & Bioengineering

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“…Adjustment of aeration rate was operated in a 50-L stirred bioreactor equipped with three turbine impellers (Zhang et al 2014). Based on the amplified standard of similar blade and linear velocity, agitation speed was set at 130 rpm in 50-L bioreactor.…”

Section: Methodsmentioning

confidence: 99%

Dissolved oxygen control strategy for improvement of TL1-1 production in submerged fermentation by Daldinia eschscholzii

Wei

Liu

Lü

2017

Bioresour. Bioprocess.

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Background2,3-Dihydro-5-hydroxy-2-methylchromen-4-one (TL1-1) is a phenolic compound with significant anti-fungal and anti-cancer activities produced by Daldinia eschscholzii (D. eschscholzii). However, studies have rarely been reported on the fermentation process of D. eschscholzii due to the urgent demand for its pharmaceutical researches and applications.ResultsIn this work, the optimal fermentation medium for improved TL1-1 yield was first obtained in a shake flask. As the fermentation process was scaling up, the marked effects of dissolved oxygen (DO) on cell growth and TL1-1 biosynthesis were observed and confirmed. Controlling a suitable DO level by the adjustment of agitation speed and aeration rate remarkably enhanced TL1-1 production in a lab-scale bioreactor. Moreover, the fermentation of D. eschscholzii was successfully applied in 500-L bioreactor, and TL1-1 production has achieved 873.63 mg/L, approximately 15.4-fold than its initial production (53.27 mg/L).ConclusionsDissolved oxygen control strategy for enhancing TL1-1 production was first proposed. Furthermore, control of the appropriate DO level has successfully performed for improving TL1-1 yield and scale-up of D. eschscholzii fermentation process.Electronic supplementary materialThe online version of this article (doi:10.1186/s40643-016-0134-4) contains supplementary material, which is available to authorized users.

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“…The overexpression of icd is expected to enhance the intracellular 2-oxoglutarate pool generated from isocitrate . 2-oxoglutarate plays a role of indicating the cellular nitrogen status, and the anticipated larger 2-oxoglutarate pool in E3::icd relative to E3 signaled nitrogen deficiency that would lead to a stimulated nitrogen metabolism (Radchenko, Thornton, & Merrick, 2013), which exerts negative effects on the biosynthesis of erythromycin (Liao et al, 2015;Zhang et al, 2014). However, the overexpression of sucBA could avoid the accumulation of 2-oxoglutarate.…”

Section: Putative Mechanisms and Promising Molecular Targets/strategies By Which E3 Enhances Its Biosynthesis Of Erythromycinmentioning

confidence: 99%

Comparative genomic and transcriptomic analysis guides to further enhance the biosynthesis of erythromycin by an overproducer

Chu³

et al. 2021

Preprint

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Omics approaches have been applied to understand the boosted productivity of natural products by industrial high-producing microorganisms. Here, with the updated genome sequence and transcriptomic profiles derived from high-throughput sequencing, we exploited comparative omics analysis to further enhance the biosynthesis of erythromycin in an industrial overproducer, Saccharopolyspora erythraea HL3168 E3. By comparing the genome of E3 with the wild type NRRL23338, we identified fragment deletions inside 56 coding sequences and 255 single nucleotide polymorphisms over the genome of E3. Substantial numbers of genomic variations were observed in genes responsible for pathways which were interconnected to the biosynthesis of erythromycin by supplying precursors/cofactors or by signal transduction. Through comparative transcriptomic analysis, L-glutamine/L-glutamate and 2-oxoglutarate were identified as reporter metabolites. Around the node of 2-oxoglutarate, genomic mutations were also observed. Furthermore, the transcriptomic data suggested that genes involved in the biosynthesis of erythromycin were significantly up-regulated constantly, whereas some genes in biosynthesis clusters of other secondary metabolites contained nonsense mutations and were expressed at extremely low levels. Based on the omics association analysis, readily available strategies were proposed to engineer E3 by simultaneously overexpressing sucB (coding for 2-oxoglutarate dehydrogenase E2 component) and sucA (coding for 2-oxoglutarate dehydrogenase E1 component), which increased the erythromycin titer by 71% compared to E3 in batch culture. This work provides more promising molecular targets to engineer for enhanced production of erythromycin by the overproducer.

show abstract

The dynamic regulation of nitrogen and phosphorus in the early phase of fermentation improves the erythromycin production by recombinant Saccharopolyspora erythraea strain

Cited by 9 publications

References 20 publications

Comparative genomic and transcriptomic analysis guides to further enhance the biosynthesis of erythromycin by an overproducer

Comparative genomic and transcriptomic analysis guides to further enhance the biosynthesis of erythromycin by an overproducer

Dissolved oxygen control strategy for improvement of TL1-1 production in submerged fermentation by Daldinia eschscholzii

Comparative genomic and transcriptomic analysis guides to further enhance the biosynthesis of erythromycin by an overproducer

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