BibTex format
@article{Micklefield:2026,
author = {Micklefield, J and Nasr, Mirza S},
journal = {Nature},
title = {Enzymatic glycosylation and amidation reshapes polyene bioactivity},
year = {2026}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Fungal diseases are an escalating threat to human health, driven by rising antimicrobial resistance and a lack of new antifungal treatments.¹‚² Polyenes, a class of complex natural products, have been widely used as antifungal agents due to their broad-spectrum activity.³ However, their clinical utility is limited by significant toxicity and poor solubility, making safer and more effective alternatives urgently needed. Previous efforts to generate improved polyenes have relied on costly, step and atom inefficient chemical syntheses., Here we describe the discovery and characterisation of pathways to previously undescribed polyenes, including unusual glycosyltransferase enzymes that introduce additional sugars onto polyene scaffolds. We also show how the reaction scope of an amidotransferase enzyme can be expanded to transform the detrimental carboxylate substituent of polyenes to alternative functionality. Introduction of a second sugar combined with carboxylate modifications leads to more potent polyene antifungals, with reduced toxicity, that are accessible by clean and efficient fermentation or enzymatic routes.
AU - Micklefield,J
AU - Nasr,Mirza S
PY - 2026///
SN - 0028-0836
TI - Enzymatic glycosylation and amidation reshapes polyene bioactivity
T2 - Nature
ER -