Metabolic engineering of Streptomyces to enhance the synthesis of valuable natural products

Xu, Zuwei; Ji, Lihao; Guo, Liang; Gao, Cong; Chen, Xiulai; Liu, Jia; Hu, Guipeng; Li, Liming

doi:10.1016/j.engmic.2022.100022

Cited by 23 publications

(20 citation statements)

References 77 publications

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“…These studies will also make great contributions to changing public health (Kwong et al, 2015), epidemiology (Llarena et al, 2017), health economics (Frank et al, 2013), and more. At present, the use of genetic engineering and other methods to modify related genes and metabolic pathways in cells to improve the yield and synthesis e ciency of speci c metabolites has become a very important way of breeding Streptomyces industrial strains (Xu et al, 2022). Sequencing, annotation and analysis of the S. fradiae genome could understand its genetic variation laws, important metabolic pathways and regulatory mechanisms at the molecular level, and provide a theoretical basis for the construction of high-yielding strains.…”

Section: Discussionmentioning

confidence: 99%

Point mutation of V252 in Neomycin C epimerase enlarges substrate binding pocket and improve the accumulation of Neomycin B in Streptomyces fradiae

Wang

et al. 2022

Preprint

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Neomycin, aminoglycoside antibiotics with broad-spectrum antibacterial resistance, is widely used in pharmaceutical and agricultural fields. However, the separation and purification process of neomycin B as an active substance is complicated in Streptomyces fradiae. Although NeoN can catalyze neomycin C to generate neomycin B, the catalytic mechanism of NeoN is still unclear. In this study, whole genomics sequencing clarified the genomic information of high-yielding mutant SF-2. Subsequently, the mechanism of NeoN in catalyzing neomycin C synthesis of neomycin B was resolved based on the NeoN-SAM-neomycin C ternary complex. Finally, mutant NeoNV252A improved the activity of NeoN and the recombinant strain SF-2-NeoNV252A accumulated neomycin B 16766.6 U/mL and the ratio of neomycin C decreased from 16.1–6.28% relative to the starting strain SF-2. In summary, this work had analyzed the catalytic mechanism of NeoN, which had certain reference significance for rationally design NeoN to improve the production of neomycin B and weaken the proportion of neomycin C.

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Section: Discussionmentioning

confidence: 99%

Point mutation of V252 in Neomycin C epimerase enlarges substrate binding pocket and improve the accumulation of Neomycin B in Streptomyces fradiae

Wang

et al. 2022

Preprint

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“…Mutant screening is an efficient strategy to enhance the production of chemicals in Actinomycetes, which mainly includes physical, chemical, and iterative mutagenesis [ 27 ]. ARTP, 60 Co-γ, and UV irradiation are typical strategies for physical mutagenesis, causing changes in molecular structure and altering production performance [ 28 ].…”

Section: Application Of Filamentous Bacteria As Microbial Cell Factoriesmentioning

confidence: 99%

Microbial cell factories based on filamentous bacteria, yeasts, and fungi

Ding

2023

Microb Cell Fact

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Background Advanced DNA synthesis, biosensor assembly, and genetic circuit development in synthetic biology and metabolic engineering have reinforced the application of filamentous bacteria, yeasts, and fungi as promising chassis cells for chemical production, but their industrial application remains a major challenge that needs to be solved. Results As important chassis strains, filamentous microorganisms can synthesize important enzymes, chemicals, and niche pharmaceutical products through microbial fermentation. With the aid of metabolic engineering and synthetic biology, filamentous bacteria, yeasts, and fungi can be developed into efficient microbial cell factories through genome engineering, pathway engineering, tolerance engineering, and microbial engineering. Mutant screening and metabolic engineering can be used in filamentous bacteria, filamentous yeasts (Candida glabrata, Candida utilis), and filamentous fungi (Aspergillus sp., Rhizopus sp.) to greatly increase their capacity for chemical production. This review highlights the potential of using biotechnology to further develop filamentous bacteria, yeasts, and fungi as alternative chassis strains. Conclusions In this review, we recapitulate the recent progress in the application of filamentous bacteria, yeasts, and fungi as microbial cell factories. Furthermore, emphasis on metabolic engineering strategies involved in cellular tolerance, metabolic engineering, and screening are discussed. Finally, we offer an outlook on advanced techniques for the engineering of filamentous bacteria, yeasts, and fungi.

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“…Lipstatin is isolated from the Streptomyces toxytricini by different extraction methods [3]. The primary function of a drug is to inhibit the absorption of fat in the intestine of a person's body [4, 5]. Blockage of lipase enzyme by orlistat/lipstatin leads to undigested triglycerides in faeces and the drug is systematically absorbed in the gastrointestinal tract.…”

Section: Introductionmentioning

confidence: 99%

Development of a thin‐layer chromatographic method for detection of lipstatin produced by Streptomyces toxytricini

Jatain

Kumar

Dubey

et al. 2023

Separation Science Plus

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Lipstatin or its saturated analog (orlistat), being the irreversible inhibitor of intestinal lipase, is widely used for the treatment of obesity. The bacterium Streptomyces toxytricini is the main source for the production of lipstatin/orlistat. There are continuous attempts to increase the production of lipstatin in S. toxytricini. For optimization of best conditions/strains for lipstatin production, there are requirements for a fast, simple, and reliable method to detect/estimate lipstatin. At present, highly sophisticated methods such as high‐performance liquid chromatography, mass spectrometry, and so forth are available for the detection and estimation of lipstatin/orlistat. These methods are very costly, time‐consuming, and require state of the art facility. Here we report a simple, fast, cost‐effective method based on thin‐layer chromatography for the detection of lipstatin in S. toxytricini. The optimized mobile phase was acetone: ethanol in a ratio of 3:7. Development of thin‐layer chromatography was done by ρ‐anisaldehyde staining that showed the pink color to the silica plate and greenish‐blue color to the lipstatin/orlistat drug. Conclusively, here we mention a simple and reproducible method of detection of orlistat and lipstatin samples extracted from S. toxytricini.

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Metabolic engineering of Streptomyces to enhance the synthesis of valuable natural products

Cited by 23 publications

References 77 publications

Point mutation of V252 in Neomycin C epimerase enlarges substrate binding pocket and improve the accumulation of Neomycin B in Streptomyces fradiae

Point mutation of V252 in Neomycin C epimerase enlarges substrate binding pocket and improve the accumulation of Neomycin B in Streptomyces fradiae

Microbial cell factories based on filamentous bacteria, yeasts, and fungi

Development of a thin‐layer chromatographic method for detection of lipstatin produced by Streptomyces toxytricini

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