2023
DOI: 10.21203/rs.3.rs-3096488/v1
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Mycoplanecins, potent anti-tuberculosis antibiotics: Elucidation of unusual biosynthesis and DnaN-targeting mode of action

Abstract: DNA polymerase III sliding clamp (DnaN) was recently validated as a new anti-tuberculosis target employing griselimycins. Three (2S,4R)-4-methylproline moieties of methylgriselimycin play significant roles in target binding and metabolic stability. Here, we identify the mycoplanecin biosynthetic gene cluster by genome mining using bait genes from the 4-methylproline pathway. We isolate and structurally elucidate four mycoplanecins comprising scarce homo-amino acids and 4-alkylprolines. Evaluating mycoplanecin … Show more

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