Optimization of media and culture conditions for the production of tacrolimus by Streptomyces tsukubaensis in shake flask and fermenter level

Patel, Gopal; Khobragade, Taresh P.; Avaghade, Sachin R.; Patil, Mahesh D.; Nile, Shivraj Hariram; Kai, Guoyin; Banerjee, Uttam Chand

doi:10.1016/j.bcab.2020.101803

Cited by 13 publications

(6 citation statements)

References 41 publications

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“…An increase in medium depth and volume could negatively regulate oxygen diffusion and antibacterial production; finally, optimum conditions were achieved in a 50 mL fermentation medium below or above which production tapers down. OVAT optimization with RSM helps to construct the best suitable parameters for optimum fermentation yield [ 30 , 31 ]…”

Section: Discussionmentioning

confidence: 99%

Production of Bioactive Compounds with Broad Spectrum Bactericidal Action, Bio-Film Inhibition and Antilarval Potential by the Secondary Metabolites of the Endophytic Fungus Cochliobolus sp. APS1 Isolated from the Indian Medicinal Herb Andrographis paniculata

2022

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Endophytes, being the co-evolution partners of green host plants, are factories of pharmaceutically valuable novel natural products. Cochliobolus sp. APS1, an endophyte of Andrographis paniculata (Green Chiretta), produces a plethora of natural bioactive compounds and the multipotent alkaloid Aziridine, 1-(2-aminoethyl)-, is the prime one among them. The isolate exhibited antibacterial, anti-biofilm, and antilarval potency. The MIC and MBC values of the ethyl-acetate culture extract ranged from 15.62 to 250 µg/mL against ten pathogenic microorganisms (including MRSA and VRSA). Killing kinetics data along with the leakage of macromolecules into the extracellular environment supports the cidal activity of the antibacterial principles. The broad spectrum antibacterial activity of Aziridine, 1-(2-aminoethyl)-, was optimized by a one-variable-at-a-time system coupled with response surface methodology, which led to a 45% enhancement of the antibacterial activity. The maximum response (22.81 ± 0.16 mm of zone of inhibition against MRSA) was marked in 250 mL Erlenmeyer flask containing 90 mL potato dextrose broth supplemented with (g%/L) glucose, 9.7; urea concentration, 0.74; with medium pH 6.48; after 8.76 days of incubation at 26 °C. APS1 strongly inhibited biofilm formation in the tested pathogenic microorganisms and acts as a larvicidal agent against the Dengue-vector Aedes aegypti. This is probably the first report of Aziridine, 1-(2-aminoethyl)-, from any endophytic source. Cochliobolus sp. APS1 possesses industrial importance for the production of bioactive alkaloids.

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Section: Discussionmentioning

confidence: 99%

Production of Bioactive Compounds with Broad Spectrum Bactericidal Action, Bio-Film Inhibition and Antilarval Potential by the Secondary Metabolites of the Endophytic Fungus Cochliobolus sp. APS1 Isolated from the Indian Medicinal Herb Andrographis paniculata

2022

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“…The ultimate outcomes of the biocatalytic cascade comprising more than a single whole-cell catalyst are often challenged by the mass transfer limitations ( Patil et al, 2017 ; Patel et al, 2020 ). However, a single wholecell catalyst expressing multiple enzymes is easy to handle and less laborious, therefore reduced the overall cost of the enzymatic process and more importantly circumvent the mass-transfer limitations ( Ahn et al, 2023 ).…”

Section: Resultsmentioning

confidence: 99%

Dual-function transaminases with hybrid nanoflower for the production of value-added chemicals from biobased levulinic acid

Khobragade,

Giri,

Pagar

et al. 2023

Front. Bioeng. Biotechnol.

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The U.S. Department of Energy has listed levulinic acid (LA) as one of the top 12 compounds derived from biomass. LA has gained much attention owing to its conversion into enantiopure 4-aminopentanoic acid through an amination reaction. Herein, we developed a coupled-enzyme recyclable cascade employing two transaminases (TAs) for the synthesis of (S)-4-aminopentanoic acid. TAs were first utilized to convert LA into (S)-4-aminopentanoic acid using (S)-α-Methylbenzylamine [(S)-α-MBA] as an amino donor. The deaminated (S)-α-MBA i.e., acetophenone was recycled back using a second TAs while using isopropyl amine (IPA) amino donor to generate easily removable acetone. Enzymatic reactions were carried out using different systems, with conversions ranging from 30% to 80%. Furthermore, the hybrid nanoflowers (HNF) of the fusion protein were constructed which afforded complete biocatalytic conversion of LA to the desired (S)-4-aminopentanoic acid. The created HNF demonstrated storage stability for over a month and can be reused for up to 7 sequential cycles. A preparative scale reaction (100 mL) achieved the complete conversion with an isolated yield of 62%. Furthermore, the applicability of this recycling system was tested with different β-keto ester substrates, wherein 18%–48% of corresponding β-amino acids were synthesized. Finally, this recycling system was applied for the biosynthesis of pharmaceutical important drug sitagliptin intermediate ((R)-3-amino-4-(2,4,5-triflurophenyl) butanoic acid) with an excellent conversion 82%.

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“…For example, FK506 production was dramatically increased by combinational strategies (such as random mutation, biosynthetic genes overexpression and exogenous feeding) and two high-yielding strains were constructed, with final FK506 production of 429 mg/L and 457 mg/L, respectively [ 16 , 34 ]. Basing on optimization of media and culture conditions in S. tsukubaensis NBRC 108819, FK506 production could be increased from 205 ± 22.0 to 616 ± 52.2 mg/L in a 2.5-L stirred-tank bioreactor [ 35 ]. However, there were few studies of an FK506 over-producer constructed rationally and systematically by taking both hyper-production and industrial application into consideration.…”

Section: Discussionmentioning

confidence: 99%

Improvement of FK506 production via metabolic engineering-guided combinational strategies in Streptomyces tsukubaensis

Zhang

Chen

et al. 2021

Microb Cell Fact

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Background FK506, a macrolide mainly with immunosuppressive activity, can be produced by various Streptomyces strains. However, one of the major challenges in the fermentation of FK506 is its insufficient production, resulting in high fermentation costs and environmental burdens. Herein, we tried to improve its production via metabolic engineering-guided combinational strategies in Streptomyces tsukubaensis. Results First, basing on the genome sequencing and analysis, putative competitive pathways were deleted. A better parental strain L19-2 with increased FK506 production from 140.3 to 170.3 mg/L and a cleaner metabolic background was constructed. Subsequently, the FK506 biosynthetic gene cluster was refactored by in-situ promoter-substitution strategy basing on the regulatory circuits. This strategy enhanced transcription levels of the entire FK506 biosynthetic gene cluster in a fine-tuning manner and dramatically increased the FK506 production to 410.3 mg/mL, 1.41-fold higher than the parental strain L19-2 (170.3 mg/L). Finally, the FK506 production was further increased from 410.3 to 603 mg/L in shake-flask culture by adding L-isoleucine at a final concentration of 6 g/L. Moreover, the potential of FK506 production capacity was also evaluated in a 15-L fermenter, resulting in the FK506 production of 830.3 mg/L. Conclusion From the aspects of competitive pathways, refactoring of the FK506 biosynthetic gene cluster and nutrients-addition, a strategy for hyper-production and potentially industrial application of FK506 was developed and a hyper-production strain L19-9 was constructed. The strategy presented here can be generally applicable to other Streptomyces for improvement of FK506 production and streamline hyper-production of other valuable secondary metabolites.

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Optimization of media and culture conditions for the production of tacrolimus by Streptomyces tsukubaensis in shake flask and fermenter level

Cited by 13 publications

References 41 publications

Production of Bioactive Compounds with Broad Spectrum Bactericidal Action, Bio-Film Inhibition and Antilarval Potential by the Secondary Metabolites of the Endophytic Fungus Cochliobolus sp. APS1 Isolated from the Indian Medicinal Herb Andrographis paniculata

Production of Bioactive Compounds with Broad Spectrum Bactericidal Action, Bio-Film Inhibition and Antilarval Potential by the Secondary Metabolites of the Endophytic Fungus Cochliobolus sp. APS1 Isolated from the Indian Medicinal Herb Andrographis paniculata

Dual-function transaminases with hybrid nanoflower for the production of value-added chemicals from biobased levulinic acid

Improvement of FK506 production via metabolic engineering-guided combinational strategies in Streptomyces tsukubaensis

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