Recombinant Macrocyclic Lanthipeptides Incorporating Non-Canonical Amino Acids

被引：36

作者：

Zambaldo, Claudio ^{[1
]}

Luo, Xiaozhou ^{[1
]}

Mehta, Angad P. ^{[1
]}

Schultz, Peter G. ^{[1
]}

机构：

[1] Scripps Res Inst, 10550 N Torrey Pines Rd, La Jolla, CA 92037 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2017年 / 139卷 / 34期

关键词：

LIPID-II; LANTIBIOTICS; NISIN; PEPTIDES; ANALOGS;

D O I：

10.1021/jacs.7b04159

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Nisin is a complex lanthipeptide that has broad spectrum antibacterial activity. In efforts to broaden the structural diversity of this ribosomally synthesized lantibiotic, we now report the recombinant expression of Nisin variants that incorporate noncanonical amino acids (ncAAs) at discrete positions. This is achieved by expressing the nisA structural gene, cyclase (nisC) and dehydratase (nisB), together with an orthogonal nonsense suppressor tRNA/aminoacyl-tRNA synthetase pair in Escherichia coli. A number of ncAAs with novel chemical reactivity were genetically incorporated into NisA, including an alpha-chloroacetamide-containing ncAA that allowed for the expression of Nisin variants with novel macrocyclic topologies. This methodology should allow for the exploration of lanthipeptide variants with new or enhanced activities.

引用

页码：11646 / 11649

页数：4

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