Phylogeny-Informed Synthetic Biology Reveals Unprecedented Structural Novelty in Type V Glycopeptide Antibiotics.

ABSTRACT: The rise and dissemination of glycopeptide antibiotic (GPA)-resistant pathogens in healthcare settings fuel efforts to discover GPAs that can overcome resistance. Members of the type V subclass of GPAs can evade common GPA resistance mechanisms and offer promise as new drug leads. We characterize five new type V GPAs-rimomycin-A/B/C and misaugamycin-A/B-discovered through a phylogeny-guided genome mining strategy coupled with heterologous production using our GPAHex synthetic biology platform. Rimomycin is a heptapeptide similar to kistamicin but includes an N-methyl-tyrosine at amino acid 6 (AA6) and substitutes 4-hydroxyphenylglycine for tyrosine and 3,5-dihydroxyphenylglycine at positions AA1 and AA3. Misaugamycin is characterized by an unprecedented N-C cross-link between AA2 an

SUBMITTER: Xu M 

PROVIDER: S-EPMC9136965 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature