Structure, biosynthesis, and bioactivity of nostolysamides
Enleyona Weir1, Ivan Anterola1, Wilfred A van der Donk1
1Department of Chemistry and Howard Hughes Medical Institute, University of Illinois at Urbana-Champaign, Urbana, IL, 61822, USA.
Biorxiv : the Preprint Server for Biology
|April 10, 2026
Summary
Researchers characterized nostolysamides, novel class II lanthipeptides from Nostoc punctiforme. These peptides show antibacterial and antifungal activity by disrupting cell membranes, with acylation not essential for bioactivity.
Area of Science:
- Microbiology
- Biochemistry
- Natural Products Chemistry
Background:
- Class II lanthipeptides are ribosomally synthesized and post-translationally modified peptides.
- Nostoc punctiforme PCC 73102 genome encodes putative class II lanthipeptides, termed nostolysamides, with unknown structure and bioactivity.
- Acylation of Lys side chains was identified in these novel peptides.
Purpose of the Study:
- To elucidate the structure and bioactivity of nostolysamides.
- To characterize the lanthipeptide synthetase NpuM and acetyltransferase NpuN involved in nostolysamide biosynthesis.
- To investigate the role of acylation in nostolysamide function.
Main Methods:
- Heterologous expression of nostolysamide biosynthetic genes in Escherichia coli.
- Marfey's analysis to determine stereochemistry of modified residues.
- Tandem mass spectrometry and mutagenesis for structural elucidation.
- In vitro assays for enzyme activity and bioactivity testing.
Main Results:
- Nostolysamides were produced and characterized, revealing four lanthionine/methyllanthionine rings with DL configurations.
- NpuM exhibits dual directionality (C-to-N and N-to-C) in ring formation.
- Nostolysamides display antibacterial and antifungal activity against Candida species via cell membrane disruption.
- Acylation by NpuN does not significantly impact the observed bioactivities.
Conclusions:
- Nostolysamides are a novel class of bioactive lanthipeptides with unique structural features.
- The ProcM-clade synthetase NpuM demonstrates versatile catalytic activity.
- The identified antibacterial and antifungal activities are independent of the acylation modification.
More Related Videos
09:08From a Natural Product to Its Biosynthetic Gene Cluster: A Demonstration Using Polyketomycin from Streptomyces diastatochromogenes Tü6028
Published on: January 13, 2017
17.9K
09:10Synthesis of Masarimycin, a Small Molecule Inhibitor of Gram-Positive Bacterial Growth
Published on: January 7, 2022
2.8K
Related Concept Videos
01:28Biosynthesis of Nucleic Acids
1.6K
Nucleic acid biosynthesis is a fundamental biochemical process that produces the purine and pyrimidine nucleotides essential for DNA and RNA synthesis. This pathway maintains a balanced nucleotide pool, preventing imbalances that could jeopardize genetic integrity and cellular function. Given the crucial role of nucleotides, their synthesis is tightly regulated to ensure proper cellular homeostasis.Purine BiosynthesisThe biosynthesis of purine nucleotides begins with ribose-5-phosphate, a...
1.6K
01:29Amino Acid Biosynthetic Pathways
1.7K
Amino acid biosynthesis is essential for cell growth, protein synthesis, and metabolic regulation. Cells generate essential and non-essential amino acids from metabolic intermediates to sustain vital biological functions. These intermediates originate from key metabolic pathways: glycolysis, the tricarboxylic acid (TCA) cycle, and the pentose phosphate pathway. Important precursors include α-ketoglutarate, pyruvate, oxaloacetate, phosphoenolpyruvate, and erythrose-4-phosphate, which...
1.7K
01:29Biosynthesis of Lipids
891
Microbial membranes exhibit remarkable diversity in lipid composition, reflecting evolutionary adaptations to various environmental conditions. The three domains of life—Bacteria, Archaea, and Eukarya—synthesize membrane lipids through distinct biosynthetic pathways, leading to fundamental structural differences that impact membrane stability, function, and adaptability.Fatty Acid-Based Lipids in Bacteria and EukaryaBacteria and eukaryotes share a common fatty acid biosynthesis...
891
01:26Biosynthesis of Polysaccharides
937
Polysaccharides such as glycogen and starch are synthesized from nucleoside diphosphate sugars, primarily uridine diphosphate glucose (UDPG) and adenosine diphosphate glucose (ADPG). These activated glucose donors act as key intermediates in carbohydrate metabolism and biosynthesis. UDPG primarily involves glycogen synthesis in animals and many bacteria, while ADPG plays a fundamental role in starch synthesis in plants and certain bacteria.UDPG is formed when glucose-1-phosphate reacts with...
937
01:24Biosynthesis in Bacteria
983
Biosynthesis in bacteria is a fundamental anabolic process that generates essential macromolecules, including proteins, nucleic acids, lipids, and polysaccharides. These macromolecules are critical for cellular growth, replication, and function. The process is tightly regulated and energetically linked to catabolic pathways to ensure optimal resource utilization.Biosynthetic pathways begin with precursor metabolites such as pyruvate, acetyl-CoA, and glucose-6-phosphate derived from glycolysis,...
983
01:15Antifungal Agents
81
Amphotericin B is a broad-spectrum antifungal agent that exploits structural differences between fungal and mammalian cell membranes. Its amphipathic structure—featuring a hydrophobic polyene-lactone ring and a hydrophilic region containing mycosamine and carboxylic acid groups—enables selective binding to ergosterol, a sterol predominantly found in fungal plasma membranes. This selective interaction underlies the drug’s antifungal activity, although weak binding to...
81