Effect of fructose on promoting fengycin biosynthesis in<i>Bacillus amyloliquefaciens</i>fmb-60

Lu, Hedong; Qian, Shijun; Umair, Muhammad; Jiang, Xingyi; Han, Jun; Lu, Zhaoxin

doi:10.1111/jam.13291

Cited by 29 publications

(24 citation statements)

References 49 publications

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“…Although fengycin displays the potential to be developed as a novel antifungal agent, the poor yield is the main limitation. In our previous works, it was found that B. amyloliquefaciens fmb-60 is able to enhance the yield of fengycin, and the gene expression of fen A is upregulated in modified Landy medium added with fructose (MLF) [ 15 ], which provides a feasible strategy to increase the production of fengycin. Based on the results presented in this study of iTRAQ-based proteomic analysis and quantitative real-time PCR verification, the fructose action mode in B. amyloliquefaciens includes all kinds of the pathways mentioned above, such as enhanced energy metabolism, cellular amino acid, amide, peptide and fatty acid metabolic and transport process, response to stimulus and, particularly, the improvement of biological metabolism of nucleic acids.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous genes, including codY , comA , degU and spo0A are also involved in regulating the biosynthesis of fengycin [ 14 ]. In previous works, B .amyloliquefaciens fmb-60 is able to enhance the yield of fengycin and upregulate the gene expression of fen in a modified Landy medium supplemented with fructose [ 15 ], but the regulatory mechanism of fructose on fengycin biosynthesis has not been elucidated yet. In this study, iTRAQ-based proteomic analysis was utilized to explain the mechanism of fructose on fengycin biosynthesis.…”

Section: Introductionmentioning

confidence: 99%

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iTRAQ-BASED Proteomic Analysis of the Mechanism of Fructose on Improving Fengycin Biosynthesis in Bacillus Amyloliquefaciens

RuiLi

Yang

et al. 2021

Molecules

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Fengycin, as a lipopeptide produced by Bacillus subtilis, displays potent activity against filamentous fungi, including Aspergillus flavus and Soft-rot fungus, which exhibits a wide range of potential applications in food industries, agriculture, and medicine. To better clarify the regulatory mechanism of fructose on fengycin biosynthesis, the iTRAQ-based proteomic analysis was utilized to investigate the differentially expressed proteins of B. amyloliquefaciens fmb-60 cultivated in ML (without fructose) and MLF (with fructose) medium. The results indicated that a total of 811 proteins, including 248 proteins with differential expression levels (162 which were upregulated (fold > 2) and 86, which were downregulated (fold <0.5) were detected, and most of the proteins are associated with cellular metabolism, biosynthesis, and biological regulation process. Moreover, the target genes’ relative expression was conducted using quantitative real-time PCR to validate the proteomic analysis results. Based on the results of proteome analysis, the supposed pathways of fructose enhancing fengycin biosynthesis in B. amyloliquefaciens fmb-60 can be summarized as improvement of the metabolic process, including cellular amino acid and amide, fatty acid biosynthesis, peptide and protein, nucleotide and nucleobase-containing compound, drug/toxin, cofactor, and vitamin; reinforcement of peptide/protein translation, modification, biological process, and response to a stimulus. In conclusion, this study represents a comprehensive and systematic investigation of the fructose mechanism on improving fengycin biosynthesis in B. amyloliquefaciens, which will provide a road map to facilitate the potential application of fengycin or its homolog in defending against filamentous fungi.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

iTRAQ-BASED Proteomic Analysis of the Mechanism of Fructose on Improving Fengycin Biosynthesis in Bacillus Amyloliquefaciens

RuiLi

Yang

et al. 2021

Molecules

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“…It was reported that inulin could promote efficient production of bacillomycin D by significantly improving the expression of lipopeptide bacillomycin D synthetase genes and by up-regulating the related regulatory factors such as ComA, DegU, SigmaH and Spo0A [25]. Coincidentally, fructose similarly enhanced the expression of lipopeptide fengycin synthetase genes, regulatory factors (ComA, SigmaH, DegU and DegQ) and the cell division and growth related genes ( ftsZ and divIVA ), leading to increased fengycin production [36]. In this study, five single factors including both fermentation conditions and medium components were explored to select the appropriate degree, and finally it was confirmed that inulin 7 g l −1 , l -sodium glutamate 15 g l −1 , MgSO 4 0.5 g l −1 , pH 7.0 and temperature 27 °C were the appropriate one (Fig.…”

Section: Discussionmentioning

confidence: 99%

Enhanced production of antifungal lipopeptide iturin A by Bacillus amyloliquefaciens LL3 through metabolic engineering and culture conditions optimization

et al. 2019

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Background Iturins, which belong to antibiotic cyclic lipopeptides mainly produced by Bacillus sp., have the potential for application in biomedicine and biocontrol because of their hemolytic and antifungal properties. Bacillus amyloliquefaciens LL3, isolated previously by our lab, possesses a complete iturin A biosynthetic pathway as shown by genomic analysis. Nevertheless, iturin A could not be synthesized by strain LL3, possibly resulting from low transcription level of the itu operon. Results In this work, enhanced transcription of the iturin A biosynthetic genes was implemented by inserting a strong constitutive promoter C2up into upstream of the itu operon, leading to the production of iturin A with a titer of 37.35 mg l −1 . Liquid chromatography-mass spectrometry analyses demonstrated that the strain produced four iturin A homologs with molecular ion peaks at m / z 1044, 1058, 1072 and 1086 corresponding to [C 14 + 2H] 2+ , [C 15 + 2H] 2+ , [C 16 + 2H] 2+ and [C 17 + 2H] 2+ . The iturin A extract exhibited strong inhibitory activity against several common plant pathogens. The yield of iturin A was improved to 99.73 mg l −1 by the optimization of the fermentation conditions using a response surface methodology. Furthermore, the yield of iturin A was increased to 113.1 mg l −1 by overexpression of a pleiotropic regulator DegQ. Conclusions To our knowledge, this is the first report on simultaneous production of four iturin A homologs (C 14 –C 17 ) by a Bacillus strain. In addition, this study suggests that metabolic engineering in combination with culture conditions optimization may be a feasible method for enhanced production of bacterial secondary metabolites. Electronic supplementary material The online version of this article (10.1186/s12934-019-1121-1) contains supplementary material, which is available to authorized users.

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“…It was demonstrated that feeding fructose could result in flux rearrangement in primary metabolism for better providing biosynthetic precursors and stimulating the secondary metabolism in A. pretiosum (Fan et al, ). Similarly, compared to glucose and sorbitol, feeding fructose could promote the fengycin biosynthesis by improving the gene expression level, precursor supply and energy metabolism in Bacillus amyloliquefaciens fmb‐60 (Lu et al, ).…”

Section: Discussionmentioning

confidence: 99%

Rational approach to improve ansamitocin P‐3 production by integrating pathway engineering and substrate feeding in Actinosynnema pretiosum

Zhong

2018

Biotech & Bioengineering

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Ansamitocin P-3 (AP-3) produced by Actinosynnema pretiosum is an important antitumor agent for cancer treatment, but its market supply suffers from a low production titer. The role of AP-3 unusual glycolate unit supply on its biosynthesis was investigated in this work by overexpressing the responsible gene cluster asm13-17 in A. pretiosum (WT). As a result, the accumulation of AP-3 and its intermediate glyceryl-S-ACP in the asm13-17-overexpressed strain (Oasm13-17) versus WT was enhanced by 1.94 and 1.49-fold, respectively. To provide a higher supply of another precursor 3-amino-5-hydroxybenzoic acid, asmUdpg was also overexpressed in Oasm13-17 (Oasm13-17:asmUdpg), and an improved AP-3 titer of 680.5 mg/L was achieved in shake flasks. To further enhance the AP-3 titer, a rational fed-batch strategy was developed in bioreactor fermentation of Oasm13-17:asmUdpg; and by pulse feeding 15 g/L fructose and 1.64 g/L isobutanol at 60, 96, and 120 hr, the AP-3 production level reached 757.7 mg/L, which is much higher than ever reported in bioreactors. This work demonstrated that a rational approach combining precursor pathway engineering with substrate feeding was very effective in enhancing the AP-3 titer, and this enabling methodology would be helpful to industrial production of this eye-catching drug.

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Effect of fructose on promoting fengycin biosynthesis inBacillus amyloliquefaciensfmb-60

Abstract: The results identify regulatory mechanisms involved in fengycin biosynthesis and provide an effective method to enhance production of fengycin.

Cited by 29 publications

References 49 publications

iTRAQ-BASED Proteomic Analysis of the Mechanism of Fructose on Improving Fengycin Biosynthesis in Bacillus Amyloliquefaciens

iTRAQ-BASED Proteomic Analysis of the Mechanism of Fructose on Improving Fengycin Biosynthesis in Bacillus Amyloliquefaciens

Enhanced production of antifungal lipopeptide iturin A by Bacillus amyloliquefaciens LL3 through metabolic engineering and culture conditions optimization

Rational approach to improve ansamitocin P‐3 production by integrating pathway engineering and substrate feeding in Actinosynnema pretiosum

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