Leucine improves the component of isovalerylspiramycins for the production of bitespiramycin

Li, Zhenlin; Wang, Yonghong; Chu, Ju; Zhuang, Yingping; Zhang, Siliang

doi:10.1007/s00449-008-0287-4

Cited by 6 publications

(3 citation statements)

References 26 publications

(21 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For instance, valine catabolism produced the units of n-butyrate, propionate and 2-methylmalonate for the biosynthesis of spiramycin [20,21], tylosin [22] and monensin A [23]. Added leucine could affect the components of isovalerylspiramycins so that the production of bitespiramycin was improved [24]. Short-chain fatty acids derived from added amino acids were secreted into a broth culture in the growth phase, followed by microbial utilisation for the synthesis of secondary metabolites in the production phase [18].…”

Section: Introductionmentioning

confidence: 99%

Glycine feeding improves pristinamycin production during fermentation including resin for in situ separation

Zhang

Jin

Chen

et al. 2011

Bioprocess Biosyst Eng

View full text Add to dashboard Cite

Seven amino acids were tested as precursors to affect pristinamycin production by a mutant strain derived from Streptomyces pristinaespiralis ATCC25486. Of those, glycine was selected as the best precursor to facilitate both cell growth and pristinamycin production at the feeding time of 36-h incubation and the feeding rate of 0.75 g L -1 flask culture. The optimized time and concentration of glycine feeding were applied to enlarged 3-L bioreactor fermentation with a resin added at the time of 20-h fermentation for in situ separation. As a result, a combination of the glycine feeding and the added resin resulted in the maximal pristinamycin yield of 616 mg L -1 culture 12 h after glycine feeding. The yield from the combined treatment was 1.71-, 2.77-and 4.32-fold of those from the mere glycine and resin treatments and the control, respectively. Other parameters, including intracellular nucleic acid content, animo nitrogen content and pH level, during 72-h fermentation were also given in association with the pristinamycin yields in the different treatments. The results indicate that glycine feeding is an effective approach to enhance pristinamycin production in the culture of S. pristinaespiralis F213 with supplemented resin for in situ separation.

show abstract

Section: Introductionmentioning

confidence: 99%

Glycine feeding improves pristinamycin production during fermentation including resin for in situ separation

Zhang

Jin

Chen

et al. 2011

Bioprocess Biosyst Eng

View full text Add to dashboard Cite

show abstract

“…The 4″-isovaleryl group of BT originates from the l -Leucine ( l -Leu) metabolic pathway. So, branched-chain amino acids, particularly l -Leu, can significantly improve the yield of BT [5]. An effective way to develop high-producing BT strain that produces more l -Leu is to eliminate the feedback regulation caused by l -Leu itself as end product.…”

Section: Introductionmentioning

confidence: 99%

Engineering of leucine-responsive regulatory protein improves spiramycin and bitespiramycin biosynthesis

Zhang

Dai

et al. 2019

Microb Cell Fact

View full text Add to dashboard Cite

Background Bitespiramycin (BT) is produced by recombinant spiramycin (SP) producing strain Streptomyces spiramyceticus harboring a heterologous 4″-O-isovaleryltransferase gene ( ist ). Exogenous l -Leucine ( l -Leu) could improve the production of BT. The orf2 gene found from the genomic sequence of S. spiramyceticus encodes a leucine-responsive regulatory protein (Lrp) family regulator named as SSP_Lrp. The functions of SSP_Lrp and l -Leu involved in the biosynthesis of spiramycin (SP) and BT were investigated in S. spiramyceticus . Results SSP_Lrp was a global regulator directly affecting the expression of three positive regulatory genes, bsm23 , bsm42 and acyB2 , in SP or BT biosynthesis. Inactivation of SSP_Lrp gene in S. spiramyceticus 1941 caused minor increase of SP production. However, SP production of the Δ SSP_Lrp -SP strain containing an SSP_Lrp deficient of putative l -Leu binding domain was higher than that of S. spiramyceticus 1941 (476.2 ± 3.1 μg/L versus 313.3 ± 25.2 μg/L, respectively), especially SP III increased remarkably. The yield of BT in Δ SSP_Lrp- BT strain was more than twice than that in 1941-BT. The fact that intracellular concentrations of branched-chain amino acids (BCAAs) decreased markedly in the Δ SSP_Lrp -SP demonstrated increasing catabolism of BCAAs provided more precursors for SP biosynthesis. Comparative analysis of transcriptome profiles of the Δ SSP_Lrp -SP and S. spiramyceticus 1941 found 12 genes with obvious differences in expression, including 6 up-regulated genes and 6 down-regulated genes. The up-regulated genes are related to PKS gene for SP biosynthesis, isoprenoid biosynthesis, a Sigma24 family factor, the metabolism of aspartic acid, pyruvate and acyl-CoA; and the down-regulated genes are associated with ribosomal proteins, an AcrR family regulator, and biosynthesis of terpenoid, glutamate and glutamine. Conclusion SSP_Lrp in S. spiramyceticus was a negative regulator involved in the SP and BT biosynthesis. The deletion of SSP_Lrp putative l -Leu binding domain was advantageous for production of BT and SP, especially their III components. Electronic supplementary material The online version of this article (10.1186/s12934-019-1086-0) contains supplementary material, which is available to authorized users.

show abstract

“…The titer of carrimycin was improved through the ribosome engineering, but it was far from the requirement in the scale-up fermentation. Many efforts have been made to improve the production of carrimycin in Streptomyces spiramyceticus WSJ−195 in recent years, including traditional random mutagenesis [9,10], medium optimization [11], exogenous feeding strategies [12,13], fermentation process control [14], and genetic engineering [15]. Among these approaches, traditional mutagenesis is a powerful and easily operated method for strain improvement in Streptomyces, especially for microbes with less understanding of genomic information and metabolic mechanisms.…”

mentioning

confidence: 99%

Enhancement of Carrimycin Production Via Traditional Mutagenesis with Metabolic Engineering in Streptomyces Spiramyceticus 54IA

Dai

Liu

et al. 2022

Preprint

View full text Add to dashboard Cite

Background: Carrimycin is a new approved class I antibiotic in China. The novel carrimycin producing strain, Streptomyces spiramyceticus 54IA, was constructed by CRISPR-Cas9 editing system without insertion of antibiotics resistant gene. The problem of low yield limits this strain in large scale fermentation. In this study, the carrimycin production was significantly improved by strain mutagenesis coupled metabolic engineering. Results: The sspD gene is responsible for degradation of triacylglycerol to provide precursors of the polyketide biosynthesis. The extra sspD gene controlled by the promoters of pks and bsm42 genes could moderately enhance carrimycin production. The Bsm42 was identified to play a pathway-specific positive regulator for carrimycin biosynthesis. Due to production of carrimycin significantly enhanced by bsm42 overexpression, the two different length promoters of bsm42 individually ligated with two reporter genes were used to monitor bsm42 expression for screening the higher carrimycin production mutants treated by plasma and ultraviolet. 47% of the 608 selected mutants had higher fermentation titer than the starting strain. The shorter promoter of bsm42 displayed more appropriate for selection of the carrimycin production improved mutants. The F2R-15 mutant had highest titer (1010±30 μg/mL), which was about 9 times higher than that of 54IA strain. Comparative analysis of transcriptome profiles of F2R-15 mutant and 54IA strains found 158 differential expression genes with more than 2 fold-changes. The up-regulated genes were associated with macrolide precursor biosynthesis, macrolide-inactivation, antibiotics transporter, oxidative phosphorylation; while the most down-regulated genes were referring to the primary metabolites synthetic genes and biosynthetic genes of other secondary metabolites. Conclusion: These results suggested that manipulation of the positive regulatory gene bsm42 and traditional mutagenesis coupled with reporter-guided mutant selection method facilitated selection of carrimycin high-yielding mutants.

show abstract

Leucine improves the component of isovalerylspiramycins for the production of bitespiramycin

Cited by 6 publications

References 26 publications

Glycine feeding improves pristinamycin production during fermentation including resin for in situ separation

Glycine feeding improves pristinamycin production during fermentation including resin for in situ separation

Engineering of leucine-responsive regulatory protein improves spiramycin and bitespiramycin biosynthesis

Enhancement of Carrimycin Production Via Traditional Mutagenesis with Metabolic Engineering in Streptomyces Spiramyceticus 54IA

Contact Info

Product

Resources

About