Generation of New Glycoanalogues of Polyene Antibiotics by Synthetic Biology—Testing Current Technical Boundaries
Abstract
:1. Introduction
2. Results
2.1. Studies on Extending Glycosyltransferases That Function in Biosynthesis of Disaccharide-Containing Polyenes
2.2. Modifying Mycosamine Residues by Combining Enzymatic Glycosylation of the C4′ Hydroxyl with Chemical Glycosylation of the C3′ Amino Group
2.3. Attempts to Glycosylate the C35 Hydroxyl Group of Amphotericin B and Analogues
2.4. Aglycone Feeding
2.5. Expression of gloDI and eurDI-DII-N-M Genes in S. nodosus ΔamphDI-NM and S. nodosus ΔamphDI-DII-NM
3. Discussion
4. Materials and Methods
4.1. Microbial Strains
4.2. DNA Methods
4.3. Polyene Extractions
4.4. Aglycone Feeding
4.5. HPLC
4.6. Mass Spectrometry
4.7. Chemical Glycosylation of 67-121C
4.8. Tests for Antifungal Activity
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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Polyene | Molecular Formula | Calc. for [M + H]+ | Observed |
---|---|---|---|
67-121A | C59H86N2019 | 1127.5903 | 1127.5891 |
67-121C | C65H96N2024 | 1289.6431 | 1289.6421 |
Glucose-modified 67-121C | C71H106N2029 | 1451.6960 | 1451.6932 |
Lactose-modified 67-121A | C71H106N2029 | 1451.6960 | 1451.6953 |
Lactose-modified 67-121C | C77H116N2O34 | 1613.7488 | 1613.7484 |
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Hogan, M.; Song, Y.; Muldoon, J.; Caffrey, P. Generation of New Glycoanalogues of Polyene Antibiotics by Synthetic Biology—Testing Current Technical Boundaries. SynBio 2024, 2, 31-55. https://doi.org/10.3390/synbio2010003
Hogan M, Song Y, Muldoon J, Caffrey P. Generation of New Glycoanalogues of Polyene Antibiotics by Synthetic Biology—Testing Current Technical Boundaries. SynBio. 2024; 2(1):31-55. https://doi.org/10.3390/synbio2010003
Chicago/Turabian StyleHogan, Mark, Yuhao Song, Jimmy Muldoon, and Patrick Caffrey. 2024. "Generation of New Glycoanalogues of Polyene Antibiotics by Synthetic Biology—Testing Current Technical Boundaries" SynBio 2, no. 1: 31-55. https://doi.org/10.3390/synbio2010003