Related Experiment Video
Updated: May 23, 2026
11:56
Antimicrobial Peptides Produced by Selective Pressure Incorporation of Non-canonical Amino Acids
Published on: May 4, 2018
An engineered lantibiotic synthetase that does not require a leader peptide on its substrate
Trent J Oman1, Patrick J Knerr, Noah A Bindman
1Howard Hughes Medical Institute and Roger Adams Laboratory, Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, Illinois 61801, USA.
Journal of the American Chemical Society
|April 7, 2012
Summary
Researchers developed a method to modify peptides without needing a leader peptide. This technique enhances the bioengineering of modified peptides, including novel lacticin 481 analogs with non-proteinogenic amino acids.
Area of Science:
- Biochemistry
- Natural Products Chemistry
- Synthetic Biology
Background:
- Ribosomally synthesized and post-translationally modified peptides are a growing class of natural products.
- Biosynthesis typically involves modifying a core peptide guided by an N-terminal leader peptide.
- Leader peptides facilitate enzyme activity but require removal, complicating bioengineering.
Purpose of the Study:
- To develop a novel bioengineering strategy for modified peptides.
- To overcome limitations associated with leader peptides in peptide biosynthesis.
- To create improved lacticin 481 analogs using non-proteinogenic amino acids.
Main Methods:
- Fusing the leader peptide of lacticin 481 to its biosynthetic enzyme, LctM.
- Enabling LctM to modify core peptides lacking a leader sequence.
- Utilizing this method for the synthesis of novel peptide analogs.
Main Results:
- Demonstrated that the fused leader peptide-enzyme construct can act on leaderless core peptides.
- Successfully prepared lacticin 481 analogs containing non-proteinogenic amino acids.
- Established a new approach for peptide bioengineering.
Conclusions:
- The developed methodology simplifies the bioengineering of modified peptides.
- This approach facilitates the production of novel peptide structures with tailored properties.
- Opens avenues for the discovery and production of new peptide-based natural products and therapeutics.
More Related Videos
Related Concept Videos
01:23Inhibitors of Gram-positive Cell Wall Synthesis
Bacterial cell walls are typically rigid structures composed mainly of peptidoglycan, a mesh-like polymer that provides mechanical strength and maintains cell shape. The synthesis of peptidoglycan is a crucial process in bacterial growth and serves as a primary target for many antibiotics.Mechanism of Action of Beta-Lactam AntibioticsBeta-lactam antibiotics, such as penicillin, inhibit peptidoglycan synthesis in actively growing cells. These antibiotics share a characteristic four-membered...
02:26tRNA Activation
Aminoacyl-tRNA synthetases are present in both eukaryotes and bacteria. Though eukaryotes have 20 different aminoacyl-tRNA synthetases to couple to 20 amino acids, many bacteria do not have genes for all of these aminoacyl-tRNA synthetases. Despite this, they still use all 20 amino acids to synthesize their proteins. For instance, some bacteria do not have the gene encoding the enzyme that couples glutamine with its partner tRNA. In these organisms, one enzyme adds glutamic acid to all of the...
01:30Production of Pharmaceuticals
Industrial insulin production uses genetically engineered E. coli expressing a proinsulin gene controlled by a tryptophan promoter and containing a methionine linker for later cleavage. The cells also carry ampicillin resistance for selective growth. Seed cultures are stored at −80 °C and production begins by thawing a small amount to inoculate starter cultures, which are progressively scaled to a 50,000-L bioreactor. In the bioreactor, E. coli grow in nutrient-rich media under sterile, tightly...
01:29Coordination of Gene Expression Processes in Bacteria
The DNA replication, transcription, and translation processes are intricately coupled in bacteria, allowing efficient gene expression and rapid protein synthesis. While this physical and functional coordination is advantageous, it introduces challenges that bacteria overcome through specific regulatory mechanisms.Coupling of Replication, Transcription, and TranslationThe coupling of replication, transcription, and translation is a hallmark of bacterial gene expression. As the replisome unwinds...
00:43Bacterial RNA Polymerase
Unlike eukaryotes, bacteria use a single RNA Polymerase (RNAP) to transcribe all genes. The different subunits of bacterial RNAPhave distinct functions. The multisubunit structure of the bacterial RNAP helps the enzyme to maintain catalytic function, facilitate assembly, interact with DNA and RNA, and self-regulate its activity.
In most genes, the transcription site is a single base present upstream of the coding sequence. Though RNAP is a catalytically efficient enzyme, it does not recognize...
In most genes, the transcription site is a single base present upstream of the coding sequence. Though RNAP is a catalytically efficient enzyme, it does not recognize...
01:23Types of RNA
Overview
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...