Thiopeptides are a diverse class of ribosomally synthesized and post-translationally modified peptides (RiPPs), secreted by Gram-positive bacteria such as Firmicutes and Actinomyces. These bacteria use thiopeptides to compete against other Gram-positive species, including Clostridium difficile, Staphylococcus aureus, Streptococcus pneumoniae, and Mycobacterium tuberculosis . Due to their high potency in inhibiting bacterial protein synthesis [156-158], thiopeptides are promising candidates for novel antibiotic development. For example, Novartis developed the thiopeptide derivative LFF571A by enhancing the solubility and chemical stability of the natural product GE2270 [159-161], a known potent inhibitor of the prokaryotic elongation factor thermo unstable (EFTu) . EFTu catalyzes the binding of aminoacyl-tRNA (aa-tRNA) to ribosomes , an essential step in protein translation.