2024-03-28T13:52:36Zhttps://eprints.lib.hokudai.ac.jp/dspace-oai/requestoai:eprints.lib.hokudai.ac.jp:2115/756912024-02-15T07:55:58Zhdl_2115_20045hdl_2115_139Biosynthetic Gene Cluster of a D-Tryptophan-Containing Lasso Peptide, MS-271Feng, ZhiOgasawara, YasushiNomura, Satoshi1000070264679Dairi, Tohruopen accessThis is the peer-reviewed version of the following article: Z. Feng, Y. Ogasawara, S. Nomura, T. Dairi, ChemBioChem 2018, 19, 2045. , which has been published in final form at https://doi.org/10.1002/cbic.201800315. This article may be used for non-commercial purposes in accordance with Wiley-VCH Terms and Conditions for Self-Archiving.antibioticsbiosynthesisD-amino acidsepimeraseslasso peptidesMS-271, produced by Streptomyces sp. M-271, is a lasso peptide natural product comprising 21 amino acid residues with a D-tryptophan at its C terminus. Because lasso peptides are ribosomal peptides, the biosynthesis of MS-271, especially the mechanism of D-Trp introduction, is of great interest. The MS-271 biosynthetic gene cluster was identified by draft genome sequencing of the MS-271 producer, and it was revealed that the precursor peptide contains all 21 amino acid residues including the C-terminal tryptophan. This suggested that the D-Trp residue is introduced by epimerization. Genes for modification enzymes such as a macrolactam synthetase (mslC), precursor peptide recognition element (mslB1), cysteine protease (mslB2), disulfide oxidoreductases (mslE, mslF), and a protein of unknown function (mslH) were found in the flanking region of the precursor peptide gene. Although obvious epimerase genes were absent in the cluster, heterologous expression of the putative MS-271 cluster in Streptomyces lividans showed that it contains all the necessary genes for MS-271 production including a gene for a new peptide epimerase. Furthermore, a gene-deletion experiment indicated that MslB1, -B2, -C and -H were indispensable for MS-271 production and that some interactions of the biosynthetic enzymes were essential for the biosynthesis of MS-271.Wiley-Blackwell2018-10-04engjournal articleAMhttp://hdl.handle.net/2115/75691https://doi.org/10.1002/cbic.2018003151439-4227Chembiochem191920452048https://eprints.lib.hokudai.ac.jp/dspace/bitstream/2115/75691/1/MS-271%20manuscript.pdfapplication/pdf368.26 KB2018-10-04