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KMID : 1094720230280050874
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Biotechnology and Bioprocess Engineering
2023 Volume.28 No. 5 p.874 ~ p.886
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Decreased Lincomycin B Content by Regulating Osmotic Pressure in Fermentation of Streptomyces lincolnensis
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Shengkai Li
Liwen Zhang
Shuhong Gao
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Abstract
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Lincomycin, a clinically important antibiotic against Gram-positive bacteria, is a sulfur-containing metabolite produced by Streptomyces lincolnensis. The main problem in the fermentation is the high content of lincomycin B, which is a by-product of insufficient methylation by S-adenosylmethionine (SAM) dependent methyltransferase. In this study, the content of lincomycin B was decreased from 4.04% to 0.75% and from 8.20% to 5.78% by the addition of NaCl as an osmotic regulator in flask and 15 L bioreactor fermentation, respectively. By analysis of the sulfur-containing metabolites (cysteine, homocysteine, SAM, and ergothioneine) and high-throughput RNA sequencing, the mechanism of osmotic regulation on lincomycin fermentation was studied. The results showed that the synthesis of methyl donor (SAM) and sulfur donor of lincomycin (ergothioneine and mycothiol) were increased at the metabolite level and transcription level under osmotic stimulation; the transcription of genes involved in sulfur assimilation (tauA, ssuA1B1C1) and lincomycin biosynthesis were also up-regulated significantly. This study provides a cost-effective method to reduce lincomycin B and increase the production of lincomycin A. The mechanisms of osmotic pressure regulation on lincomycin fermentation was also elucidated, which may provide more genetically modified targets for overproduction of lincomycin and other sulfur containing secondary metabolites.
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KEYWORD
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Streptomyces lincolnensis, lincomycin, osmotic pressure, sulfur metabolite, transcriptome analysis
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