Utilization of glycerol as cysteine and carbon sources for cephalosporin C production by Acremonium chrysogenum M35 in methionine-unsupplemented culture

Shin, Hyun Yong; Lee, Jin Young; Park, Chulhwan; Kim, Seung Wook

doi:10.1016/j.jbiotec.2010.12.021

Cited by 5 publications

(4 citation statements)

References 28 publications

(29 reference statements)

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“…M icroorganisms are increasingly being utilized for the commercial production of a variety of products, such as fine chemicals (1,2), health products (3,4), pharmaceuticals (5,6), and biofuels (7,8). An important factor affecting the product price is the cost of the sugar feedstock (9,10).…”

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confidence: 99%

Effects of Reduced and Enhanced Glycogen Pools on Salt-Induced Sucrose Production in a Sucrose-Secreting Strain of Synechococcus elongatus PCC 7942

Qiao

Duan

Zhang

et al. 2018

Appl Environ Microbiol

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Sucrose and glycogen syntheses in cyanobacteria share the common precursor glucose-1-phosphate. It is generally assumed that lowering glycogen synthesis could drive more carbon toward sucrose synthesis that can be induced by salt stress among cyanobacteria. By using a theophylline-dependent riboswitch system, the expression of , a key gene in glycogen synthesis, was downregulated in a quantitative manner in a sucrose-secreting strain of PCC 7942. We observed that the stepwise suppression of glycogen synthesis limited rather than stimulated sucrose production in the salt-stressed cells, suggesting that glycogen could serve as a carbon pool for the synthesis of sucrose. Accordingly, we generated glycogen-overproducing strains, but the increased glycogen pool alone did not stimulate sucrose production, indicating that alternative steps limit the carbon flux toward the synthesis of sucrose. Consistent with previous studies that showed that sucrose-phosphate synthase (SPS) catalyzes the rate-limiting step in sucrose synthesis, the combination of glycogen overproduction and overexpression resulted in increased sucrose production. Our results indicate that the glycogen and sucrose pools are closely linked in PCC 7942, and we propose that enhancing the glycogen pool could be a promising strategy for the improvement of sucrose production by cyanobacteria in the presence of a strong sucrose synthesis sink. Many cyanobacteria naturally synthesize and accumulate sucrose when stressed by NaCl, which provides novel possibilities for obtaining sugar feedstock by engineering of cyanobacteria. It has been assumed that glycogen synthesis competes with sucrose synthesis for the carbon flux. However, our results showed that the suppression of glycogen synthesis decreased rather than stimulated sucrose production in a sucrose-secreting strain of PCC 7942. This result suggests that glycogen could serve as a supportive rather than a competitive carbon pool for the synthesis of sucrose, providing new insights about the relation between glycogen synthesis and sucrose synthesis in cyanobacteria. This finding is also useful to guide metabolic engineering work to optimize the production of sucrose and possibly other products by cyanobacteria.

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confidence: 99%

Effects of Reduced and Enhanced Glycogen Pools on Salt-Induced Sucrose Production in a Sucrose-Secreting Strain of Synechococcus elongatus PCC 7942

Qiao

Duan

Zhang

et al. 2018

Appl Environ Microbiol

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“…Glycerol-supplemented cultures show concise growth curves and reasonable CPC production, while the maximum points of CPC production are lower than that of recovered xylose culture. Glycerol serves as a strong electron donor for growth and secondary metabolites production and supports cysteine synthesis in the pathway, directly, as 3-phosphoglycerate, a glycerol metabolite, is a precursor of cysteine (Lane et al, 2018;Shin et al, 2011;Usher et al, 1992). Formulating a complex media including the undefined xylose media and glycerol may result in cocktail effects on microbial cultures and can make up for the longer culture time issue of xylose-supplemented culture (Oh et al, 2019a(Oh et al, , 2019b.…”

Section: Feasibility Of the Undefined Media For Cephalosporin C Produ...mentioning

confidence: 99%

Undefined xylose media extracted from biorefinery waste for enhanced and eco‐friendly production of cephalosporin C by Acremonium chrysogenumM35

Kim

et al. 2023

GCB Bioenergy

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Xylose‐rich undefined broth, extracted from the dilute acid pretreatment wastes of barley straw, serves as resourceful media for Acremonium chrysogenum M35 culture and production of cephalosporin C (CPC). Concentrating the extract with proper reprocessing enables to prepare various concentrations of xylose broth (2%–8%). The undefined xylose media were prepared for CPC production from A. chrysogenum M35 by the addition of other nutrients. Cell growth and CPC production were the most effective at 6% xylose and additional 2% glycerol, with maximum CPC production of 9.07 g/L after 6 days, which is higher production than that in defined media prepared with laboratory‐level nutrients and reagents. Investigation of autotrophic and reverse trans‐sulfuration pathways for cysteine synthesis, a limited element of three precursors for CPC synthesis, supports the enhanced CPC production in undefined media. Abundance of xylose ensures a maintained NADPH concentration required for sulfate reduction and synthesis of amino sulfide such as cysteine. Cystathionine‐γ‐lyase activity profiling indicated more efficient biosynthesis in undefined media than in other cultures use glycerol and glucose, and the biosynthesis pathway of CPC production by the cephalosporin gene cluster (i.e. pcbC and cefG genes) was investigated. The process using undefined xylose media was designed, and process simulation program confirmed our results.

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“…Nevertheless, there are still a lot of recent publications on improvement of CPC-producing strain by traditional methods, such as UV [6] or NTG [7] mutagenesis, and optimization of fermentation process [8] . More recently, glycerol was found can be used in the fermentation broth [9] , [10] replacing methionine that Dr. Arnold Demain used decades ago, to stimulate the biosynthesis of CPC. Researchers also tried solid-state and submerged fermentation of CPC [11] besides the traditional production.…”

Section: Biosynthesis Of Cpcmentioning

confidence: 99%

Study on genetic engineering of Acremonium chrysogenum , the cephalosporin C producer

Zhu

2016

Synthetic and Systems Biotechnology

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Acremonium chrysogenum is an important filamentous fungus which produces cephalosporin C in industry. This review summarized the study on genetic engineering of Acremonium chrysogenum, including biosynthesis and regulation for fermentation of cephalosporin C, molecular techniques, molecular breeding and transcriptomics of Acremonium chrysogenum. We believe with all the techniques available and full genomic sequence, the industrial strain of Acremonium chrysogenum can be genetically modified to better serve the pharmaceutical industry.

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Utilization of glycerol as cysteine and carbon sources for cephalosporin C production by Acremonium chrysogenum M35 in methionine-unsupplemented culture

Cited by 5 publications

References 28 publications

Effects of Reduced and Enhanced Glycogen Pools on Salt-Induced Sucrose Production in a Sucrose-Secreting Strain of Synechococcus elongatus PCC 7942

Effects of Reduced and Enhanced Glycogen Pools on Salt-Induced Sucrose Production in a Sucrose-Secreting Strain of Synechococcus elongatus PCC 7942

Undefined xylose media extracted from biorefinery waste for enhanced and eco‐friendly production of cephalosporin C by Acremonium chrysogenumM35

Study on genetic engineering of Acremonium chrysogenum , the cephalosporin C producer

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