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Review
. 2021 Jul 29:9:692466.
doi: 10.3389/fbioe.2021.692466. eCollection 2021.

Mining and Biosynthesis of Bioactive Lanthipeptides From Microorganisms

Caiyun Li  1 , Khorshed Alam  1 , Yiming Zhao  1 , Jinfang Hao  1 , Qing Yang  2 , Youming Zhang  1 , Ruijuan Li  1 , Aiying Li  1
Affiliations
Review

Mining and Biosynthesis of Bioactive Lanthipeptides From Microorganisms

Caiyun Li et al. Front Bioeng Biotechnol. .

Abstract

Antimicrobial resistance is one of the most serious public health issues in the worldwide and only a few new antimicrobial drugs have been discovered in recent decades. To overcome the ever-increasing emergence of multidrug-resistant (MDR) pathogens, discovery of new natural products (NPs) against MDR pathogens with new technologies is in great demands. Lanthipeptides which are ribosomally synthesized and post-translationally modified peptides (RiPPs) display high diversity in their chemical structures and mechanisms of action. Genome mining and biosynthetic engineering have also yielded new lanthipeptides, which are a valuable source of drug candidates. In this review we cover the recent advances in the field of microbial derived lanthipeptide discovery and development.

Keywords: biosynthesis; genome mining; lanthipeptide; natural product; pathway engineering.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Structures of representative lanthipeptides.
FIGURE 2
FIGURE 2
Formation of unusual amino acid residues and action targets of lanthipeptides. (A) Unusual amino acid residues in the lanthipeptides. (B) Two main action targets of lanthipeptides. (C) Formation of characteristic lanthionine (Lan) or methyllanthionine (MetLan). Firstly, Ser/Thr-OH is dehydrated and followed by Cys-SH nucleophilic attack and cyclization. In class I lanthipeptide, Ser/Thr-OH is activated by glutamination at the presence of tRNAGlu, followed by deglutamination and dehydration while in class II-IV, Ser/Thr-OH is phosphorylated by LanM/LanKC/LanL and then undergoes dephosphorylation and dehydration. In addition, the labionin in the class III structure is formed by the nucleophilic attack of another Dha enol anion (Ren et al., 2020). It is speculated that class V is also dehydrated through phosphorylation and dephosphorylation mechanisms.
FIGURE 3
FIGURE 3
Biosynthetic pathways of lanthipeptides. (A) The general steps of lanthipeptide biosynthesis. (B) Five classes of key enzymes for the formation of thioether ring. (C) Representative BGCs for lanthipeptide biosynthesis.
FIGURE 4
FIGURE 4
Scheme of genome mining of lanthipeptides.
See this image and copyright information in PMC

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