Lantibiotics are ribosomally synthesized and post-translationally modified peptide natural products. The biosynthetic enzymes that convert peptide substrates into constrained antibiotics are not well understood. Here, we seek to carry out biochemical and structural biological studies on several of these enzymes and address questions regarding substrate recognition, substrate tolerance, and the potential of this system for engineering efforts to generate molecules that are not found in nature.
This research plan focuses on understanding how simple peptides can be transformed into potent bacteriocidal agents. Knowledge gained from this proposal will further benefit the development of this powerful class of antibiotics.
|An, Linna; Cogan, Dillon P; Navo, Claudio D et al. (2018) Substrate-assisted enzymatic formation of lysinoalanine in duramycin. Nat Chem Biol 14:928-933|
|Morita, Maho; Hao, Yue; Jokela, Jouni K et al. (2018) Post-Translational Tyrosine Geranylation in Cyanobactin Biosynthesis. J Am Chem Soc 140:6044-6048|
|Ortega, Manuel A; Cogan, Dillon P; Mukherjee, Subha et al. (2017) Two Flavoenzymes Catalyze the Post-Translational Generation of 5-Chlorotryptophan and 2-Aminovinyl-Cysteine during NAI-107 Biosynthesis. ACS Chem Biol 12:548-557|
|Sardar, Debosmita; Hao, Yue; Lin, Zhenjian et al. (2017) Enzymatic N- and C-Protection in Cyanobactin RiPP Natural Products. J Am Chem Soc 139:2884-2887|
|Repka, Lindsay M; Chekan, Jonathan R; Nair, Satish K et al. (2017) Mechanistic Understanding of Lanthipeptide Biosynthetic Enzymes. Chem Rev 117:5457-5520|
|Hao, Yue; Pierce, Elizabeth; Roe, Daniel et al. (2016) Molecular basis for the broad substrate selectivity of a peptide prenyltransferase. Proc Natl Acad Sci U S A 113:14037-14042|
|Ortega, Manuel A; Hao, Yue; Walker, Mark C et al. (2016) Structure and tRNA Specificity of MibB, a Lantibiotic Dehydratase from Actinobacteria Involved in NAI-107 Biosynthesis. Cell Chem Biol 23:370-380|
|Tang, Weixin; Dong, Shi-Hui; Repka, Lindsay M et al. (2015) Applications of the class II lanthipeptide protease LicP for sequence-specific, traceless peptide bond cleavage. Chem Sci 6:6270-6279|
|Dong, Shi-Hui; Tang, Weixin; Lukk, Tiit et al. (2015) The enterococcal cytolysin synthetase has an unanticipated lipid kinase fold. Elife 4:|
|Ortega, Manuel A; Hao, Yue; Zhang, Qi et al. (2015) Structure and mechanism of the tRNA-dependent lantibiotic dehydratase NisB. Nature 517:509-12|
Showing the most recent 10 out of 16 publications