Butremycin, the 3-Hydroxyl Derivative of Ikarugamycin and a Protonated Aromatic Tautomer of 5′-Methylthioinosine from a Ghanaian Micromonospora sp. K310

Kyeremeh, Kwaku; Acquah, Kojo Sekyi; Sazak, Anil; Houssen, Wael E.; Tabudravu, Jioji N.; Deng, Hai; Jaspars, Marcel

doi:10.3390/md12020999

Cited by 43 publications

(40 citation statements)

References 22 publications

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“…Based on their unique biosynthetic origins, PTMs have multiple biological activities that involve antiprotozoal1415, antifungal71516, antibacterial91718 and antiviral actions19. They also inhibit cholesteryl ester accumulation in J774 macrophages14.…”

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confidence: 99%

Structural diversity of anti-pancreatic cancer capsimycins identified in mangrove-derived Streptomyces xiamenensis 318 and post-modification via a novel cytochrome P450 monooxygenase

Jiang

et al. 2017

Sci Rep

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Polycyclic tetramate macrolactams (PTMs) were identified as distinct secondary metabolites of the mangrove-derived Streptomyces xiamenensis 318. Together with three known compounds—ikarugamycin (1), capsimycin (2) and capsimycin B (3)—two new compounds, capsimycin C (4) with trans-diols and capsimycin D (5) with trans-configurations at C-13/C-14, have been identified. The absolute configurations of the tert/tert-diols moiety was determined in 4 by NMR spectroscopic analysis, CD spectral comparisons and semi-synthetic method. The post-modification mechanism of the carbocyclic ring at C-14/C-13 of compound 1 in the biosynthesis of an important intermediate 3 was investigated. A putative cytochrome P450 superfamily gene, SXIM_40690 (ikaD), which was proximally localized to the ikarugamycin biosynthetic pathway, was characterized. In vivo gene inactivation and complementation experiment confirmed that IkaD catalysed the epoxide-ring formation reaction and further hydroxylation of ethyl side chain to form capsimycin G (3′). Binding affinities and kinetic parameters for the interactions between ikarugamycin (1) and capsimycin B (3) with IkaD were measured with Surface Plasmon Resonance. The intermediate compound 3′ was isolated and identified as 30-hydroxyl-capsimycin B. The caspimycins 2 and 3, were transferred to methoxyl derivatives, 6 and 7, under acidic and heating conditions. Compounds 1–3 exhibited anti-proliferative activities against pancreatic carcinoma with IC50 values of 1.30–3.37 μM.

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confidence: 99%

Structural diversity of anti-pancreatic cancer capsimycins identified in mangrove-derived Streptomyces xiamenensis 318 and post-modification via a novel cytochrome P450 monooxygenase

Jiang

et al. 2017

Sci Rep

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“…This results support findings reported by Kyeremeh el al. 26 on fractions containing micromonospora for which only two showed antimicrobial activity. The fraction NKLS 6 2 was selected for HPLC analysis and the result revealed four peaks ( Figure 6).…”

Section: Discussionmentioning

confidence: 99%

Isolation of antibiotic Producing Microorganisms from some water bodies within Eastern and Greater Accra Regions of Ghana

Amiteye

Dayie

Gbedema

et al. 2019

Preprint

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Background: Most antimicrobial agents used today are isolated and extracted from microbial source. The emergence of antimicrobial resistance and need for better, broad spectrum antimicrobial agent is always in high demand. In this study, a total of 112 aquatic microbial isolates from 14 sample sites of water bodies in Ghana were screened by agar-well diffusion method for the ability of antimicrobial metabolites.Results: Out of these antibacterial activities, 10 inhibited the growth of at least one test microorganism with zones of growth inhibitions ranged between 2.5±0.5 -35.5±0.5 mm against Staphylococcus aureus (ATCC25923), Streptococcus pyogenes (clinical isolates), Escherichia coli (NCTC9002), Pseudomonas aeruginosa (ATCC27853), Neisseria gonorrhoeae (clinical isolate), Klebsiella pneumoniae (Clinical isolate), Bacillus subtilis (NCTC10073) and Salmonella typhi (NCTC 6017). The extracts of the isolates showed minimum inhibitory concentrations of which extract NKSEW 3 against Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa were 25.00, 12.50 and 25.00 mg/mL respectively while that of NKLS 6 were 12.50, 6.25 and 25.00 mg/mL. The isolates NKSEW 3 and NKLS 6 were identified to be Pseudomonas species using chromagar and biochemical tests. The GC-MS result for NKLS 6 2 (a fraction obtained from NKLS 6 ) revealed five compounds including; Tridecanal, 17-octadecanal, ethanol, 2-(9-octadecenyloxy)-, (Z), 2pentadecanone, 6, 10, 14-trimethyl diisooctyl phthalate and 17-octadecanal (C 18 H 34 O) as good pharmacological agents. Conclusion:Microorganisms isolated from water bodies in Ghana have the potential of producing antimicrobial agents.

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“…An additional peak of interest ( m/z 495) was detected in the Δ cftA mutant. This was tentatively identified as butremycin, a known C25-hydroxyl derivative of ikarugamycin 24 . The experimental mass matches the compound and its UV profile is consistent with other PTMs.…”

Section: Figurementioning

confidence: 98%

Native and engineered clifednamide biosynthesis in multipleStreptomycesspp

Ding

Blodgett

2017

Preprint

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8Polycyclic tetramate macrolactam (PTM) natural products are produced by actinomycetes and 9 other bacteria. PTMs are often bioactive, and the simplicity of their biosynthetic clusters make 10 them attractive for bioengineering. Clifednamide-type PTMs from Streptomyces sp. JV178 contain 11 a distinctive ketone group, suggesting the existence of a novel PTM oxidizing enzyme. Here, we 12 report the new cytochrome P450 enzyme (CftA) is required for clifednamide production. Genome 13 mining was used to identify several new clifednamide producers, some having improved 14 clifednamide yields. Using a parallel synthetic biology approach, CftA isozymes were used to 15 engineer the ikarugamycin pathway of Streptomyces sp. NRRL F-2890 to yield clifednamides. 16Further, we observed that strong CftA expression leads to the production of a new PTM, 17clifednamide C. We demonstrate the utility of both genome mining and synthetic biology to rapidly 18 increase clifednamide production and identify a PTM tailoring enzyme for rational molecule

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Butremycin, the 3-Hydroxyl Derivative of Ikarugamycin and a Protonated Aromatic Tautomer of 5′-Methylthioinosine from a Ghanaian Micromonospora sp. K310

Cited by 43 publications

References 22 publications

Structural diversity of anti-pancreatic cancer capsimycins identified in mangrove-derived Streptomyces xiamenensis 318 and post-modification via a novel cytochrome P450 monooxygenase

Structural diversity of anti-pancreatic cancer capsimycins identified in mangrove-derived Streptomyces xiamenensis 318 and post-modification via a novel cytochrome P450 monooxygenase

Isolation of antibiotic Producing Microorganisms from some water bodies within Eastern and Greater Accra Regions of Ghana

Native and engineered clifednamide biosynthesis in multipleStreptomycesspp

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