Mutasynthesis of Physostigmines in <i>Myxococcus xanthus</i>
Lea Winand, Pascal Schneider, Sebastian Kruth, Nico-Joel Greven, Wolf Hiller, Marcel Kaiser, Jörg Pietruszka, Markus Nett
Abstract
The alkaloid physostigmine is an approved anticholinergic drug and an important lead structure for the development of novel therapeutics. Using a complementary approach that merged chemical synthesis with pathway refactoring, we produced a series of physostigmine analogues with altered specificity and toxicity profiles in the heterologous host Myxococcus xanthus. The compounds that were generated by applying a simple feeding strategy include the promising drug candidate phenserine, which was previously accessible only by total synthesis.
Topics & Concepts
Myxococcus xanthusChemistryPhysostigmineDrug developmentDrug discoveryCode refactoringDrugCombinatorial chemistryComputational biologyBiochemistryPharmacologyBiologyProgramming languageComputer scienceMutantAcetylcholineGeneSoftwareMicrobial Natural Products and BiosynthesisChemical Synthesis and AnalysisMarine Sponges and Natural Products