6533b862fe1ef96bd12c6128

RESEARCH PRODUCT

Structure, Biosynthesis, and Bioactivity of Photoditritide from Photorhabdus temperata Meg1

Marcel KaiserRyan Musumba AworiTill OpatzHelge B. BodeJonathan GroßLei Zhao

subject

medicine.drug_classPharmaceutical Science01 natural sciencesAnalytical Chemistrychemistry.chemical_compoundHydrolysisBiosynthesisNonribosomal peptideDrug DiscoverymedicinePharmacologychemistry.chemical_classificationbiology010405 organic chemistryOrganic ChemistryTrypanosoma brucei rhodesiensebiology.organism_classificationCyclic peptide0104 chemical sciencesAmino acid010404 medicinal & biomolecular chemistryComplementary and alternative medicinechemistryBiochemistryAntiprotozoalMolecular MedicineMicrococcus luteus

description

A new cyclic peptide photoditritide (1), containing two rare amino acid d-homoarginine residues, was isolated from Photorhabdus temperata Meg1 after the nonribosomal peptide synthetase encoding gene pdtS was activated via promoter exchange. The structure of 1 was elucidated by HR-MS and NMR experiments. The absolute configurations of amino acids were determined according to the advanced Marfey's method after hydrolysis of 1. Bioactivity testing of 1 revealed potent antimicrobial activity against Micrococcus luteus with an MIC value of 3.0 μM and weak antiprotozoal activity against Trypanosoma brucei rhodesiense with an IC50 value of 13 μM. Additionally, the biosynthetic pathway of 1 was also proposed.

https://doi.org/10.1021/acs.jnatprod.9b00932