Bioprocess and genetic engineering aspects of ascomycin production: a review

Sambyal, Krishika; Singh, Rahul Vikram

doi:10.1186/s43141-020-00092-0

Cited by 6 publications

(4 citation statements)

References 46 publications

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“…Ascomycin production, strain Streptomyces hygroscopicus var. ascomyceticusis studied well and previous scientific reports concluded that wild strain produced ascomycin in a very little amount; therefore, various yield improvement techniques are applied [19].…”

Section: Resultsmentioning

confidence: 98%

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A Group Contribution Analogy as Selection Criteria for Nutrients Fermentation Media in the Production of Tacrolimus, Sirolimus and Ascomycin

Suzin Bertan,

Fonseca,

Aurelio Cremasco

2023

IJLEMR

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Tacrolimus, sirolimus, and ascomycin are macrolides related to a decrease in the occurrence and severity of refractory rejection episodes and other diseases, such as the skin and eyes.The determination of optimum initial sources of carbon and nitrogen in the medium is an essential step in optimizing the fermentation process to obtain these drugs. The current research proposes an innovative technique as selection criteria to culture media carbon and nitrogen sources.The concept is an analogy to group contribution from thermodynamics to identify molecular fragments. Tacrolimus, sirolimus and ascomycin molecular structures and fermentation results of these macrolides were analyzed. This approach can enhance the productivity of these important immunosuppressants.

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Section: Resultsmentioning

confidence: 98%

“…Ascomycin (FK520),(Fig. 3),was initially referred to as FR-900520 and isolated from S. hygroscopicus KK317 in 1962 [19]. It was due to the high effectiveness of an orally used cyclosporin A that is a cyclic peptide accompanying 11 amino acids, which led to the discovery of this novel class of compounds.…”

Section: Introductionmentioning

confidence: 99%

A Group Contribution Analogy as Selection Criteria for Nutrients Fermentation Media in the Production of Tacrolimus, Sirolimus and Ascomycin

Suzin Bertan,

Fonseca,

Aurelio Cremasco

2023

IJLEMR

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“…Extraction of DNA from the different environments is followed by a metagenomic approach. Usually, there are two commonly applied methods to screen the construction of the metagenomic library, sequence‐based screening, and function‐based screening 38–40. Sequence‐based screening has the advantage of conserved sequence similarity assessment and functional gene annotation through online databases 41, 42.…”

Section: Trends and Strategies In Enzyme Engineering For Enzymatic Sy...mentioning

confidence: 99%

Enzymatic Catalysts for Hydroxamic Acid Formation: A Mini‐Review

Singh

2023

ChemBioEng Reviews

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In recent years, biocatalysts have emerged as crucial tool in organic synthesis, particularly for the production of drug intermediates and precursors, e.g., the synthesis of hydroxamic acids. Traditionally, hydroxamic acids were synthesized using organic chemistry methods. However, with the growing emphasis on sustainable and environment‐friendly practices, the chemical industry has increasingly turned towards green synthesis approaches. The significance of hydroxamic acids in medicinal chemistry has also contributed to the changing trends. Following the approval of certain hydroxamic acids as histone deacetylase (HDAC) inhibitors for cancer treatment by the Food and Drug Administration (US‐FDA), there has been a renewed focus on their synthesis and the development of derivatives with improved properties. As an alternative route, amidases have emerged as promising biocatalysts for hydroxamic acid synthesis through their acyltransferase activity. Recent advancements in the synthesis approaches for hydroxamic acids are reviewed. The biocatalytic routes are explored, emphasizing the use of amidases and their acyltransferase activity. The scope and potential applications of this chemoenzymatic approach in synthesizing various hydroxamic acids and their derivatives are discussed. Such advancements have the potential to revolutionize the production of these important compounds, making the synthesis process more sustainable, efficient, and economically viable.

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“…ascomyceticus ATCC 14891 [ 1 ]. Because of its specific structure, FK520 exhibits diverse biological and pharmacological activities, including antifungal [ 2 ], antimalarial [ 3 ], immunosuppressive [ 4 ] and anticonvulsive effects [ 5 ]. Therefore, FK520 has shown broad application prospect in the clinical treatment of organ transplant rejections, skin diseases and autoimmune diseases [ 2 , 6 , 7 ].…”

Section: Introductionmentioning

confidence: 99%

Enhanced ascomycin production in Streptomyces hygroscopicus var. ascomyceticus by employing polyhydroxybutyrate as an intracellular carbon reservoir and optimizing carbon addition

et al. 2021

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Background Ascomycin is a multifunctional antibiotic produced by Streptomyces hygroscopicus var. ascomyceticus. As a secondary metabolite, the production of ascomycin is often limited by the shortage of precursors during the late fermentation phase. Polyhydroxybutyrate is an intracellular polymer accumulated by prokaryotic microorganisms. Developing polyhydroxybutyrate as an intracellular carbon reservoir for precursor synthesis is of great significance to improve the yield of ascomycin. Results The fermentation characteristics of the parent strain S. hygroscopicus var. ascomyceticus FS35 showed that the accumulation and decomposition of polyhydroxybutyrate was respectively correlated with cell growth and ascomycin production. The co-overexpression of the exogenous polyhydroxybutyrate synthesis gene phaC and native polyhydroxybutyrate decomposition gene fkbU increased both the biomass and ascomycin yield. Comparative transcriptional analysis showed that the storage of polyhydroxybutyrate during the exponential phase accelerated biosynthesis processes by stimulating the utilization of carbon sources, while the decomposition of polyhydroxybutyrate during the stationary phase increased the biosynthesis of ascomycin precursors by enhancing the metabolic flux through primary pathways. The comparative analysis of cofactor concentrations confirmed that the biosynthesis of polyhydroxybutyrate depended on the supply of NADH. At low sugar concentrations found in the late exponential phase, the optimization of carbon source addition further strengthened the polyhydroxybutyrate metabolism by increasing the total concentration of cofactors. Finally, in the fermentation medium with 22 g/L starch and 52 g/L dextrin, the ascomycin yield of the co-overexpression strain was increased to 626.30 mg/L, which was 2.11-fold higher than that of the parent strain in the initial medium (296.29 mg/L). Conclusions Here we report for the first time that polyhydroxybutyrate metabolism is beneficial for cell growth and ascomycin production by acting as an intracellular carbon reservoir, stored as polymers when carbon sources are abundant and depolymerized into monomers for the biosynthesis of precursors when carbon sources are insufficient. The successful application of polyhydroxybutyrate in increasing the output of ascomycin provides a new strategy for improving the yields of other secondary metabolites.

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Bioprocess and genetic engineering aspects of ascomycin production: a review

Cited by 6 publications

References 46 publications

A Group Contribution Analogy as Selection Criteria for Nutrients Fermentation Media in the Production of Tacrolimus, Sirolimus and Ascomycin

A Group Contribution Analogy as Selection Criteria for Nutrients Fermentation Media in the Production of Tacrolimus, Sirolimus and Ascomycin

Enzymatic Catalysts for Hydroxamic Acid Formation: A Mini‐Review

Enhanced ascomycin production in Streptomyces hygroscopicus var. ascomyceticus by employing polyhydroxybutyrate as an intracellular carbon reservoir and optimizing carbon addition

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