Two newly identified enzymes let Imperial College London researchers rework polyene antifungals into novel compounds that were often more potent than nystatin and less toxic than amphotericin B in early tests.
One enzyme added the sugar L-digitoxose to several polyenes, while another altered a toxicity-linked carboxyl group; the team also moved the gene cluster into another bacterium as a first step toward scalable fermentation.
Nys34, the lead compound from the series, outperformed amphotericin B against a drug-resistant Aspergillus fumigatus strain in some lab tests, reduced the fungus in mice, and showed lower toxicity in human cells.
The advance targets a thin drug pipeline—WHO says only four antifungals won FDA approval from 2014 to 2024—even as resistance rises and researchers seek safer replacements for kidney-damaging amphotericin B.
Micklefield has filed a patent and is seeking industry partners to develop Nys34, while outside researchers said the work could open a broader enzyme toolkit for fermenting customized polyene drugs at scale.