Heterologous expression reveals a cryptic morphogenetic lanthipeptide durhapeptin from Streptomyces durhamensis

Area of Science:

• Microbiology
• Molecular Biology
• Biochemistry

Background:

• Morphological differentiation in Streptomyces is governed by extracellular peptide signals.
• Class III lanthipeptides, like SapB and AmfS, are key regulators of this process.

Purpose of the Study:

• To identify and characterize novel class III lanthipeptides involved in Streptomyces morphological differentiation.
• To investigate the function and specificity of a newly discovered lanthipeptide, durhapeptin.

Main Methods:

• Genome mining of Streptomyces durhamensis to identify a novel lanthipeptide gene cluster.
• Heterologous expression of the precursor peptide and modifying enzyme in Escherichia coli.
• Mass spectrometry and partial hydrolysis for structural analysis of durhapeptin.
• Functional assays to assess the morphogenetic activity of durhapeptin variants.

Main Results:

• A new class III lanthipeptide, durhapeptin, was identified and produced via heterologous expression.
• Durhapeptin contains two labionin cross-links, confirmed by mass spectrometry and hydrolysis.
• Durhapeptin selectively induced aerial hyphae formation in specific Streptomyces species.
• Hydrophobicity of durhapeptin residues is critical for its morphogenetic activity.

Conclusions:

• Cryptic class III lanthipeptides play a role in species-specific regulation of Streptomyces morphological differentiation.
• Durhapeptin highlights the importance of this lanthipeptide class in bacterial developmental biology.
• The findings underscore the potential of lanthipeptides in understanding and manipulating bacterial development.