Malacidin: Difference between revisions
the source is referring to a hypothetical future medication based on this discovery |
Ahwchemistry (talk | contribs) Added chembox to begin adding details about this molecule. |
||
| Line 1: | Line 1: | ||
[[File:Malacidins.tif|320px|thumb|Chemical structure of malacidin A and B]] |
[[File:Malacidins.tif|320px|thumb|Chemical structure of malacidin A and B]]{{Chembox |
||
| Name = |
|||
| ImageFile = |
|||
| OtherNames = |
|||
| IUPACName = |
|||
| SystematicName = |
|||
|Section1={{Chembox Identifiers |
|||
| SMILES = CC(NC([C@@H]1C[C@@H](CN1C([C@H](NC([C@@H](NC(CNC([C@H](NC([C@H](NC([C@H](NC([C@@H](N2)C(C)C)=O)CCCCN)=O)C(C(O)=O)O)=O)CC(O)=O)=O)=O)C(C)C(O)=O)=O)C(C)C)=O)C)=O)[C@@H](NC([C@H](NC(/C=C/C=C\CCC(C)C)=O)C(C)C(O)=O)=O)C2=O |
|||
| InChI = InChI=1S/C56H88N12O20/c1-25(2)17-13-11-12-14-19-35(69)62-40(29(8)54(83)84)50(79)66-42-31(10)59-47(76)34-21-28(7)24-68(34)53(82)39(27(5)6)65-49(78)41(30(9)55(85)86)63-36(70)23-58-45(74)33(22-37(71)72)61-52(81)43(44(73)56(87)88)67-46(75)32(18-15-16-20-57)60-48(77)38(26(3)4)64-51(42)80/h11-12,14,19,25-34,38-44,73H,13,15-18,20-24,57H2,1-10H3,(H,58,74)(H,59,76)(H,60,77)(H,61,81)(H,62,69)(H,63,70)(H,64,80)(H,65,78)(H,66,79)(H,67,75)(H,71,72)(H,83,84)(H,85,86)(H,87,88)/b12-11-,19-14+/t28-,29?,30?,31?,32+,33+,34-,38-,39+,40+,41-,42+,43+,44?/m0/s1 |
|||
}} |
|||
| Section2 = {{Chembox Properties}} |
|||
| Section3 = {{Chembox Structure}} |
|||
| Section4 = {{Chembox Pharmacology}} |
|||
| Section5 = |
|||
| Section6 = |
|||
}} |
|||
'''Malacidins''' are a class of [[antibiotics]] found in soil [[microbiome]]s but not reported in [[microbiological culture]]-based studies. The discovery of malacidins was formally reported in 2018.<ref name = "Hover_2018">{{cite journal | last1=Hover|first1=Bradley M.|last2=Kim|first2=Seong-Hwan|last3=Katz|first3=Micah|last4=Charlop-Powers|first4=Zachary|last5=Owen|first5=Jeremy G.|last6=Ternei|first6=Melinda A.|last7=Maniko|first7=Jeffrey|last8=Estrela|first8=Andreia B.|last9=Molina|first9=Henrik|last10=Park|first10=Steven|last11=Perlin|first11=David S.|last12=Brady|first12=Sean F.| name-list-format = vanc | display-authors = 6 | title=Culture-independent discovery of the malacidins as calcium-dependent antibiotics with activity against multidrug-resistant Gram-positive pathogens|journal=[[Nature Microbiology]]|date=12 February 2018|doi=10.1038/s41564-018-0110-1}}</ref> |
'''Malacidins''' are a class of [[antibiotics]] found in soil [[microbiome]]s but not reported in [[microbiological culture]]-based studies. The discovery of malacidins was formally reported in 2018.<ref name = "Hover_2018">{{cite journal | last1=Hover|first1=Bradley M.|last2=Kim|first2=Seong-Hwan|last3=Katz|first3=Micah|last4=Charlop-Powers|first4=Zachary|last5=Owen|first5=Jeremy G.|last6=Ternei|first6=Melinda A.|last7=Maniko|first7=Jeffrey|last8=Estrela|first8=Andreia B.|last9=Molina|first9=Henrik|last10=Park|first10=Steven|last11=Perlin|first11=David S.|last12=Brady|first12=Sean F.| name-list-format = vanc | display-authors = 6 | title=Culture-independent discovery of the malacidins as calcium-dependent antibiotics with activity against multidrug-resistant Gram-positive pathogens|journal=[[Nature Microbiology]]|date=12 February 2018|doi=10.1038/s41564-018-0110-1}}</ref> |
||
Revision as of 15:37, 14 February 2018
| Identifiers | |
|---|---|
3D model (JSmol)
|
|
| |
| |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
| |
Malacidins are a class of antibiotics found in soil microbiomes but not reported in microbiological culture-based studies. The discovery of malacidins was formally reported in 2018.[1]
Chemical structure
The malacidins are cyclic lipopeptides differing only by a methylene at their lipid tails.[1] Their peptide cores include four non-proteinogenic amino acids.[1] The name "malacidin" is a shortening of the full name "metagenomic acidic lipopeptide antibiotic-cidins."[2]
Malacidins are distantly related to the class of daptomycin antibiotics.[2] The malacidins have been classified as calcium-dependent antibiotics (CDA); these antibiotics only become active against bacteria in the presence of calcium, and otherwise inert.[1][3] The discovery of the malacidins supported the view that the calcium-dependent antibiotics are a larger than previously thought class.[1]
Discovery
Malacidins were discovered by researchers at Rockefeller University, led by Drs. Brad Hover and Sean Brady. The group had been looking into antibiotics related to daptomycin and their calcium-dependent nature, but determined that it would be impractical to culture variations in lab conditions.[2] Instead, the team used gene sequencing to study micro-organisms from nearly two thousand soil samples taken across the United States, as to evaluate the types of antibotics these micro-organisms generate to sustain themselves within the harsh soil conditions. Their analysis showed the malacidins appearing in more than 19% of the samples. They were able to determine the relevant DNA from organisms that produced these antibiotics, insert these into a host, and generate sufficient quantities of malacidins for further testing.[2] The work was first published as a letter in Nature Microbiology in February 2018.[1][4] The approach of "mining" the soil for antibiotics has the potential to discover further classes of antibiotics that otherwise cannot be developed under laboratory conditions.[3]
Mechanism of action
Malacidins act by a calcium-dependent interaction with Lipid II, a bacterial cell wall precursor molecule; such interactions should not affect the cell walls of a host body and make the antibiotics non-toxic to the host.[1][3] Brady's team believes that the calcium dependence for malacidins helps prevent microbes from evolving resistance to the antibiotic.[3]
Potential applications
The malacidins were shown to fight multidrug-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA) skin infections in an animal wound model.[1] They were also found not to produce antibiotic resistance under laboratory conditions.[1] However, malacidins were shown to treat only Gram-positive infections.[1]
References
- ^ a b c d e f g h i j Hover, Bradley M.; Kim, Seong-Hwan; Katz, Micah; Charlop-Powers, Zachary; Owen, Jeremy G.; Ternei, Melinda A.; et al. (12 February 2018). "Culture-independent discovery of the malacidins as calcium-dependent antibiotics with activity against multidrug-resistant Gram-positive pathogens". Nature Microbiology. doi:10.1038/s41564-018-0110-1.
{{cite journal}}: Unknown parameter|name-list-format=ignored (|name-list-style=suggested) (help) - ^ a b c d Healy, Melissa (13 February 2018). "In soil-dwelling bacteria, scientists find a new weapon to fight drug-resistant superbugs". Los Angeles Times. Retrieved 13 February 2018.
{{cite web}}: Unknown parameter|name-list-format=ignored (|name-list-style=suggested) (help) - ^ a b c d Kaplan, Sarah (February 13, 2018). "A potentially powerful new antibiotic is discovered in dirt". The Washington Post. Retrieved February 13, 2018.
- ^ "New antibiotic family discovered in dirt". BBC. 13 February 2018. Retrieved 13 February 2018.