Polyene antimycotic
{{Short description|Class of antifungal compounds}}
Polyene antimycotics, sometimes referred to as polyene antibiotics, are a class of antimicrobial polyene compounds that target fungi.{{cite book|chapter-url=https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=mmed&part=A4050|title=Polyene Antifungal Drugs|website=NCBI Bookshelf|year=1996|publisher=The University of Texas Medical Branch at Galveston|access-date=29 January 2010|isbn=9780963117212|chapter=Antifungal Agents|pmid=21413319 |last1=Baron |first1=S. |last2=Dixon |first2=D. M. |last3=Walsh |first3=T. J. }} These polyene antimycotics are typically obtained from certain species of Streptomyces bacteria. Previously, polyenes were thought to bind to ergosterol in the fungal cell membrane, weakening it and causing leakage of K+ and Na+ ions, which could contribute to fungal cell death. However, more detailed studies of polyene molecular properties have challenged this model suggesting that polyenes instead bind and extract ergosterol directly from the cellular membrane thus disrupting the many cellular functions ergosterols perform.{{cite journal |last1=Thomas M |first1=Anderson |last2=Clay C |first2=Mary |last3=Cioffi G |first3=Alexander |last4=Diaz A |first4=Katrina |last5=Hisao S |first5=Grant |last6=Turrle D |first6=Marcus |last7=Nieuwkoop J |first7=Andrew |last8=Comellas |first8=Gemma |last9=Maryum |first9=Nashrah |last10=Wang |first10=Shu |last11=Uno E |first11=Bruce |last12=Wildeman L |first12=Erin |last13=Tamir |first13=Gonene |last14=Rienstra M |first14=Chad |last15=Burke D |first15=Martub |title=Amphotericin forms an extramembranous and fungicidal sterol sponge |journal=Nature Chemical Biology |date=Mar 30, 2014 |volume=10 |issue=5 |pages=400–406 |doi=10.1038/nchembio.1496 |pmid=24681535 |pmc=3992202 }}{{Cite journal|last1=Robbins|first1=Nicole|last2=Caplan|first2=Tavia|last3=Cowen|first3=Leah E.|author-link3=Leah E. Cowen|date=September 8, 2017|title=Molecular Evolution of Antifungal Drug Resistance|journal=Annual Review of Microbiology|volume=71|pages=753–775|doi=10.1146/annurev-micro-030117-020345|issn=1545-3251|pmid=28886681|doi-access=free}} Amphotericin B, nystatin, and natamycin are examples of polyene antimycotics. They are a subgroup of macrolides.{{cite journal |title=Chemistry and Biology of the Polyene Macrolide Antibiotics |last=Hamilton-Miller |journal=Bacteriological Reviews |year=1973 |volume=37 |issue=2 |publisher=American Society for Microbiology |pages=166–196 |doi=10.1128/BR.37.3.166-196.1973 |pmc=413810 |pmid=4578757}}
Structures
Their chemical structures feature a large ring of atoms (in essence, a cyclic ester ring) containing multiple conjugated carbon-carbon double bonds (hence polyene) on one side of the ring and multiple hydroxyl groups bonded to the other side of the ring. Their structures also often have a D-mycosamine (a type of amino-glycoside) group bonded to the molecule.{{cite journal|doi=10.1046/j.1432-1033.2002.03147.x|title=Solution NMR structure of five representative glycosylated polyene macrolide antibiotics with a sterol-dependent antifungal activity|journal=European Journal of Biochemistry|volume=269|issue=18|pages=4533–4541|year=2002|last1=Volpon|first1=Laurent|last2=Lancelin|first2=Jean-Marc|pmid=12230565|doi-access=free}} The series of conjugated double bonds typically absorbs strongly in the ultraviolet-visible region of the electromagnetic spectrum, often resulting in the polyene antibiotics having a yellow color.
Image:Amphotericin B new.svg. Amphotericin B is an example of a yellow polyene antimycotic agent. Note the alternating double and single bonds in the center and the mycosamine group in the bottom-right corner.]]
Image:Natamycin.svg, sometimes called pimaricin.]]
Biosynthesis
The natural route to synthesis includes polyketide synthase components.{{cite journal|title=A labile point in mutant amphotericin polyketide synthases|vauthors=Khan N, Rawlings B, Caffrey P | journal=Biotechnol. Lett. |date=Jan 26, 2011|pmid= 21267757|doi=10.1007/s10529-011-0538-3|volume=33|issue=6|pages=1121–6|s2cid=10209476 |url=https://hal.archives-ouvertes.fr/hal-00663072/document}}
Other examples of polyenes
References
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{{Antifungals}}
{{antimicrobial-stub}}