期刊
ACS SYNTHETIC BIOLOGY
卷 10, 期 10, 页码 2579-2591出版社
AMER CHEMICAL SOC
DOI: 10.1021/acssynbio.1c00224
关键词
lanthipeptide; lanthipeptide synthetase; Synechococcus; heterologous expression; lanthipeptide production
资金
- European Union Horizon 2020 Research and Innovation Programme under the MarieSklodowska-Curie grant agreement (ALERT Program) [713482]
- NWO-NACTAR program [16433]
Lanthipeptides are ribosomally synthesized and post-translationally modified peptides characterized by stability and functionality provided by lanthionine rings. Heterologous expression of lanthipeptide biosynthetic enzymes offers a system for designing and producing new lanthipeptides with biotechnological or clinical properties. SyncM from marine cyanobacteria has been identified as a promiscuous enzyme with relaxed substrate specificity for producing diverse lanthipeptides.
Lanthipeptides are ribosomally synthesized and post-translationally modified peptides characterized by the presence of lanthionine rings that provide stability and functionality. Genome mining techniques have shown their huge diversity and potential for the discovery of novel active molecules. However, in many cases, they are not easily produced under laboratory conditions. The heterologous expression of these molecules using well-characterized lanthipeptide biosynthetic enzymes is rising as an alternative system for the design and production of new lanthipeptides with biotechnological or clinical properties. Nevertheless, the substrate-enzyme specificity limits the complete modification of the desired peptides and hence, their full stability and/or biological activity. New low substrate-selective biosynthetic enzymes are therefore necessary for the heterologous production of new-to-nature peptides. Here, we have identified, cloned, and heterologously expressed in Lactococcus lactic the most promiscuous lanthipeptide synthetase described to date, i.e., SyncM from the marine cyanobacteria Synechococcus MITS9509. We have characterized the functionality of SyncM by the successful expression of 15 out of 18 different SyncA substrates, subsequently determining the dehydration and cydization processes in six representatives of them. This characterization highlights the very relaxed substrate specificity of SyncM toward its precursors and the ability to catalyze the formation of exceptionally large rings in a variety of topologies. Our results suggest that SyncM could be an attractive enzyme to design and produce a wide variety of new-to-nature lanthipeptides with a broad range of ring topologies.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据