Heterologous\nBiosynthesis of New Lanthipeptides Nocardiopeptins\nwith an Unprecedented Bridging Pattern of Lanthionine and Labionin

The class III lanthipeptide synthetase (LanKC) installs\nunusual\namino acids, such as lanthionine and labionin, in lanthipeptides.\nThrough genome mining, we discovered a new class III lanthipeptide\nsynthetase coding gene (<i>nptKC</i>) and precursor peptide\ncoding genes (<i>nptA1</i>, <i>nptA2</i>, and <i>nptA3</i>) in the genome of the actinobacterium <i>Nocardiopsis\nalba</i>. Coexpression experiments of the biosynthetic genes\nin <i>Escherichia coli</i> resulted in the production of\nnew lanthipeptides named nocardiopeptins A1-A3. Analysis of two-dimensional\nNMR spectra after enzymatic degradation and partial basic hydrolysis\nof nocardiopeptin A2 revealed that labionin was located in lanthionine\nwith opposite orientations, forming a nesting structure in nocardiopeptin\nA2. To the best of our knowledge, this bridging pattern in the lanthipeptides\nwas unprecedented, indicating a novel reaction characteristic of the\nclass III lanthipeptide synthetase NptKC.