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Streptide is a newly discovered macrocyclic naturally occurring streptococcal peptide.
Streptococcal bacteria are thought to use peptides as communication signals. Often these types of peptides contain unusual post-translational modifications. Many different biosynthetic strategies for the formation of cyclic peptides have now been observed in nature. Several cyclization reactions in which the N-terminal end is connected to the C-terminal end of the peptides have been well documented. Other biosynthetic cyclization types have also been observed, such as using isopeptide bonds, disulfide bonds, esters and thiolactones. However, the biosynthesis of the newly reported streptide peptide does not fall into any of these categories. Hence, a member of a new family of cyclic peptides has been found.
Figure 1 shows the chemical structure of streptide as deduced by Schramma et al. in 2015. The research group used several tools, such as HPLC-UV purification, NMR, mass spectrometry, solid-phase peptide synthesis as well as genetic and biochemical studies to determine the structure and conformation of streptide and its biochemical synthesis.
Figure 1: The chemical structure of streptide including the stereochemistry as deduced by Schramma et al. is shown in the left part of the panel. The middle and right part of the panel shows models of the peptides generated using a simple force field method. However, a NMR based model can be reviewed in the cited paper.
Streptide is produced by the pathogen Streptococcus thermophilus and was found to have a lysine-to-tryptophan (K-W) crosslink in its peptide backbone creating a cycle in the N-terminal part of the peptide. Streptococcus thermophilus or Streptococcus salivarius subspecies thermophilus is a gram-negative bacteria. This bacteria is found in fermented milk products. It is usually used for the production of yoghurt. It has been reported that yoghurt helps alleviate symptoms of mucositis which can be caused by chemotherapy in cancer patients. Mucositis is an inflammation of the mucous membranes in the digestive system which also can cause ulcers in the digestive tract. Streptococcus thermophilus is also classified as a lactic acid bacterium and is therefore considered to be a probiotic microorganism.
Kelsey R. Schramma, Leah B. Bushin and Mohammad R. Seyedsayamdost; Structure and biosynthesis of a macrocyclic peptide containing an unprecedented lysine-to-tryptophan crosslink. Nature Chemistry 2015, vol 7, 431-437.
Whitford, E. J.; Cummins, A. G.; Butler, R. N.; Prisciandaro, L. D.; Fauser, J. K.; Yazbeck, R; Lawrence, A; Cheah, K. Y.; Wright, T. H.; Lymn, K. A.; Howarth, G. S. (2009). “Effects of Streptococcus thermophilus TH-4 on intestinal mucositis induced by the chemotherapeutic agent, 5-Fluorouracil (5-FU)”. Cancer biology & therapy 8 (6): 505–11.