Engineering Propionibacterium freudenreichii subsp. shermanii for enhanced propionic acid fermentation: Effects of overexpressing propionyl-CoA:Succinate CoA transferase

Wang, Zhongqiang; Ammar, Ehab M.; Zhang, An; Wang, Liqun; Meng, Lin; Yang, Shang‐Tian

doi:10.1016/j.ymben.2014.10.005

Cited by 61 publications

(40 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, a recent study upregulated the last step in propionic acid biosynthesis, the CoAT [68]. The native coAT gene was cloned into a replicative vector [60] under the control of a strong native promoter and used to transform P. shermanii by electroporation [15].…”

Section: Gene Overexpressionmentioning

confidence: 99%

Microbial Propionic Acid Production

et al. 2017

View full text Add to dashboard Cite

Propionic acid (propionate) is a commercially valuable carboxylic acid produced through microbial fermentation. Propionic acid is mainly used in the food industry but has recently found applications in the cosmetic, plastics and pharmaceutical industries. Propionate can be produced via various metabolic pathways, which can be classified into three major groups: fermentative pathways, biosynthetic pathways, and amino acid catabolic pathways. The current review provides an in-depth description of the major metabolic routes for propionate production from an energy optimization perspective. Biological propionate production is limited by high downstream purification costs which can be addressed if the target yield, productivity and titre can be achieved. Genome shuffling combined with high throughput omics and metabolic engineering is providing new opportunities, and biological propionate production is likely to enter the market in the not so distant future. In order to realise the full potential of metabolic engineering and heterologous expression, however, a greater understanding of metabolic capabilities of the native producers, the fittest producers, is required.

show abstract

Section: Gene Overexpressionmentioning

confidence: 99%

Microbial Propionic Acid Production

et al. 2017

View full text Add to dashboard Cite

show abstract

“…Propionibacteria are major producers of PA, owing to the vitality, high yield, wide variety of substrates used, “generally regarded as safe” designation, and antimicrobial activity (Guan et al, ). Various strategies have been developed to improve PA yield and increase productivity of propionibacteria, including optimization of carbon sources (Coral et al, ) and fermentation modes (Zhu et al, ), control of culture conditions such as pH (Zhuge et al, ) and oxidoreduction potential (Zhuge et al, ), reductions in by‐product accumulation (Zhang & Yang, ), and engineering of metabolic pathways (Liu et al, , ; Wang et al, ). Despite all of this, microbial production of PA is still unable to meet industrial standards and market demand.…”

Section: Introductionmentioning

confidence: 99%

Comparative genomics and transcriptomics analysis‐guided metabolic engineering of Propionibacterium acidipropionici for improved propionic acid production

Guan

et al. 2017

Biotech & Bioengineering

View full text Add to dashboard Cite

Acid stress induced by the accumulation of organic acids during the fermentation of propionibacteria is a severe limitation in the microbial production of propionic acid (PA). To enhance the acid resistance of strains, the tolerance mechanisms of cells must first be understood. In this study, comparative genomic and transcriptomic analyses were conducted on wild-type and acid-tolerant Propionibacterium acidipropionici to reveal the microbial response of cells to acid stress during fermentation. Combined with the results of previous proteomic and metabolomic studies, several potential acid-resistance mechanisms of P. acidipropionici were analyzed. Energy metabolism and transporter activity of cells were regulated to maintain pH homeostasis by balancing transmembrane transport of protons and ions; redundant protons were eliminated by enhancing the metabolism of certain amino acids for a relatively stable intracellular microenvironment; and protective mechanism of macromolecules were also induced to repair damage to proteins and DNA by acids. Transcriptomic data indicated that the synthesis of acetate and lactate were undesirable in the acid-resistant mutant, the expression of which was 2.21-fold downregulated. In addition, metabolomic data suggested that the accumulation of lactic acid and acetic acid reduced the carbon flow to PA and led to a decrease in pH. On this basis, we propose a metabolic engineering strategy to regulate the synthesis of lactic acid and acetic acid that will reduce by-products significantly and increase the PA yield by 12.2% to 10.31 ± 0.84 g/g DCW. Results of this study provide valuable guidance to understand the response of bacteria to acid stress and to construct microbial cell factories to produce organic acids by combining systems biology technologies with synthetic biology tools.

show abstract

“…As a result, rational design of native PA producers remains challenging. Only a few examples exist in the literature and these typically result in modest improvements and occur in lower producing native producers that are easier to engineer, such as P. shermanii [7, 8]. Furthermore, these improved strains are still inferior to the best native producers.…”

Section: Introductionmentioning

confidence: 99%

Awakening sleeping beauty: production of propionic acid in Escherichia coli through the sbm operon requires the activity of a methylmalonyl-CoA epimerase

et al. 2017

View full text Add to dashboard Cite

BackgroundPropionic acid is used primarily as a food preservative with smaller applications as a chemical building block for the production of many products including fabrics, cosmetics, drugs, and plastics. Biological production using propionibacteria would be competitive against chemical production through hydrocarboxylation of ethylene if native producers could be engineered to reach near-theoretical yield and good productivity. Unfortunately, engineering propionibacteria has proven very challenging. It has been suggested that activation of the sleeping beauty operon in Escherichia coli is sufficient to achieve propionic acid production. Optimising E. coli production should be much easier than engineering propionibacteria if tolerance issues can be addressed.ResultsPropionic acid is produced in E. coli via the sleeping beauty mutase operon under anaerobic conditions in rich medium via amino acid degradation. We observed that the sbm operon enhances amino acids degradation to propionic acid and allows E. coli to degrade isoleucine. However, we show here that the operon lacks an epimerase reaction that enables propionic acid production in minimal medium containing glucose as the sole carbon source. Production from glucose can be restored by engineering the system with a methylmalonyl-CoA epimerase from Propionibacterium acidipropionici (0.23 ± 0.02 mM). 1-Propanol production was also detected from the promiscuous activity of the native alcohol dehydrogenase (AdhE). We also show that aerobic conditions are favourable for propionic acid production. Finally, we increase titre 65 times using a combination of promoter engineering and process optimisation.ConclusionsThe native sbm operon encodes an incomplete pathway. Production of propionic acid from glucose as sole carbon source is possible when the pathway is complemented with a methylmalonyl-CoA epimerase. Although propionic acid via the restored succinate dissimilation pathway is considered a fermentative process, the engineered pathway was shown to be functional under anaerobic and aerobic conditions.Electronic supplementary materialThe online version of this article (doi:10.1186/s12934-017-0735-4) contains supplementary material, which is available to authorized users.

show abstract

Engineering Propionibacterium freudenreichii subsp. shermanii for enhanced propionic acid fermentation: Effects of overexpressing propionyl-CoA:Succinate CoA transferase

Cited by 61 publications

References 38 publications

Microbial Propionic Acid Production

Microbial Propionic Acid Production

Comparative genomics and transcriptomics analysis‐guided metabolic engineering of Propionibacterium acidipropionici for improved propionic acid production

Awakening sleeping beauty: production of propionic acid in Escherichia coli through the sbm operon requires the activity of a methylmalonyl-CoA epimerase

Contact Info

Product

Resources

About