Midecamycin Is Inactivated by Several Different Sugar Moieties at Its Inactivation Site
Abstract
:1. Introduction
2. Results
2.1. Expression and Purification of GTs
2.2. Glucosylation of Midecamycin
2.3. OleD-Mediated Glycodiversificaion of Midecamycin
2.4. Protein Engineering of OleD to Enhance Its Catalytic Efficiencies
2.5. Water Solubility of Midecamycin 2′-O-Glucopyranoside
2.6. Antimicrobial Activities of Midecamycin 2′-O-Glycosides
3. Discussion
4. Materials and Methods
4.1. Chemicals
4.2. Plasmids and Strains
4.3. Protein Expression and Purification
4.4. Glycosylation Assays
4.5. Condition Optimization for OleD-Catalyzed Reactions
4.6. Molecular Docking of Ligands with Proteins
4.7. Directed Mutations of OleD
4.8. Water Solubility Assay
4.9. Evaluation of Antimicrobial Activity of Midecamycin 2′-O-Glycosides
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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1a | 1c | |||
---|---|---|---|---|
Position | δC | δH (mult, J Hz) | δC | δH (mult, J Hz) |
1 | 172.3 | 172.2 | ||
2 | 37.9 | 2.65 (dd, 12.3, 12.0) | 37.9 | 2.65 (overlap) |
2.41 (dd, 13.2, 5.4) | 2.37 (dd, 12.3, 7.6) | |||
3 | 71.1 | 5.09–5.14 (m) | 71.1 | 5.08–5.13 (m) |
4 | 85.7 | 3.54 (dd, 10.2, 6.0) | 85.9 | 3.38 (overlap) |
5 | 76.8 | 3.87 (overlap) | 76.3 | 3.89 (overlap) |
6 | 30.2 | 2.13–2.21 (m) | 30.1 | 2.14–2.23 (m) |
7 | 31.6 | 1.48–1.56 (m) | 32.6 | 1.52–1.61 (m) |
1.07–1.13 (m) | 0.98–1.03 (m) | |||
8 | 35.2 | 1.86–1.95 (m) | 35.1 | 1.92–2.00 (m) |
9 | 74.1 | 4.23 (dd, 9.6, 5.4) | 74.1 | 4.22 (dd, 9.6, 7.6) |
10 | 128.8 | 5.64 (dd, 15.6, 9.6) | 128.6 | 5.65 (dd, 15.3, 5.8) |
11 | 136.6 | 6.58 (dd, 16.0, 10.2) | 136.7 | 6.59 (dd, 15.2, 10.4) |
12 | 133.9 | 6.10 (dd,15.0, 10.8) | 133.8 | 6.11 (dd, 14.9, 10.6) |
13 | 133.2 | 5.71–5.78 (m) | 133.3 | 5.71–5.79 (m) |
14 | 41.8 | 2.13–2.21 (m) | 42.8 | 2.47–2.51 (m) |
2.45–2.50 (m) | 2.16–2.22 (m) | |||
15 | 70.6 | 4.94 (dd, 13.8, 6.6) | 70.7 | 4.93 (dd, 10.0, 6.5) |
16 | 20.6 | 1.25 (d, 6.0) | 20.9 | 1.27 (d, 5.6) |
17 | 43.5 | 2.82–2.90 (m) | 43.4 | 2.83 (dd, 18.6, 11.3) |
2.36 (dd, 18.0, 7.8) | 2.36 (overlap) | |||
18 | 203.5 | 9.66 (s) | 203.5 | 9.66 (s) |
19 | 15.3 | 0.99 (t, 5.4) | 15.3 | 0.99 (d, 5.2) |
20 | 175.8 | 175.8 | ||
21 | 28.5 | 2.43–2.49 (m) | 28.5 | 2.41–2.49 (m) |
22 | 9.6 | 1.19 (overlap) | 9.6 | 1.19 (overlap) |
23 | 62.9 | 3.62 (s) | 62.5 | 3.58 (s) |
1′ | 102.7 | 4.69 | 102.1 | 4.69 (d, 7.1) |
2′ | 82.3 | 3.42 (dd, 7.8, 6.0) | 81.5 | 3.48 (dd, 8.9, 5.6) |
3′ | 69.7 | 2.87 (overlap) | 69.9 | 2.98 (overlap) |
4′ | 80.4 | 3.63 (overlap) | 78.5 | 3.70 (dd, 9.6, 7.3) |
5′ | 73.5 | 3.54–3.60 (m) | 73.5 | 3.52–3.56 (m) |
6′ | 19.3 | 1.34 (d, 6.0) | 19.3 | 1.36 (d, 6.2) |
7′ and 8′ | 41.8 | 2.59(s) | 41.9 | 2.68 (s) |
1″ | 99.0 | 5.16 (overlap) | 98.7 | 5.17 (overlap) |
2″ | 43.0 | 2.06 (d, 15.0) | 42.8 | 2.06 (dd, 14.5, 4.6) |
1.96 (dd, 14.4, 4.8) | 1.97 (d, 14.1) | |||
3″ | 70.4 | 70.6 | ||
4″ | 78.6 | 4.60 (d, 10.2) | 78.5 | 4.62 (d, 9.8) |
5″ | 65.0 | 4.43–4.47 (m) | 65.1 | 4.37 (overlap) |
6″ | 17.9 | 1.11 (s) | 17.9 | 1.13 (d, 2.3) |
7″ | 26.8 | 1.13 (s) | 26.5 | 1.14 (s) |
8″ | 175.8 | 175.8 | ||
9″ | 28.3 | 2.45 (overlap) | 28.3 | 2.46 (overlap) |
10″ | 9.6 | 1.20 | 9.6 | 1.21 (overlap) |
1‴ | 107.8 | 4.40 (dd, 7.8, 7.2) | 107.8 | 4.88 (d, 7.8) |
2‴ | 76.5 | 3.21 (dd, 8.4, 8.4) | 76.1 | 3.21 (dd, 9.0, 7.6) |
3‴ | 77.8 | 3.38 (dd, 9.0, 9.0) | 78.0 | 3.35 (overlap) |
4‴ | 71.3 | 3.34 (overlap) | 71.1 | 3.46 (overlap) |
5‴ | 78.5 | 3.29 (overlap) | 67.5 | 3.90 (overlap) |
3.2 (overlap) | ||||
6‴ | 62.9 | 3.89 (overlap) | ||
3.76 (dd, 12.0, 4.8) |
Substrate | Km (mM) | Vmax (mM/min) |
---|---|---|
UDP-Glc | 1.933 ± 0.124 | 0.080 ± 0.002 |
midecamycin | 0.626 ± 0.106 | 11.120 ± 0.830 |
Strain | MIC (μg/mL) | |||
---|---|---|---|---|
Midecamycin | 1a | 1c | 1g | |
Bacillus intestinalis strain T30 | 0.5 | — | — | — |
Bacillus subtilis strain 168 | 1 | — | — | — |
Staphylococcus aureus | 1 | — | — | — |
Streptococcus pneumoniae | 0.25 | — | — | — |
Pseudomonas aeruginosa PAO1 | — | — | — | — |
Escherichia coli DH5α | — | — | — | — |
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Lin, R.; Hong, L.-L.; Jiang, Z.-K.; Li, K.-M.; He, W.-Q.; Kong, J.-Q. Midecamycin Is Inactivated by Several Different Sugar Moieties at Its Inactivation Site. Int. J. Mol. Sci. 2021, 22, 12636. https://doi.org/10.3390/ijms222312636
Lin R, Hong L-L, Jiang Z-K, Li K-M, He W-Q, Kong J-Q. Midecamycin Is Inactivated by Several Different Sugar Moieties at Its Inactivation Site. International Journal of Molecular Sciences. 2021; 22(23):12636. https://doi.org/10.3390/ijms222312636
Chicago/Turabian StyleLin, Ru, Li-Li Hong, Zhong-Ke Jiang, Ke-Meng Li, Wei-Qing He, and Jian-Qiang Kong. 2021. "Midecamycin Is Inactivated by Several Different Sugar Moieties at Its Inactivation Site" International Journal of Molecular Sciences 22, no. 23: 12636. https://doi.org/10.3390/ijms222312636