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RiPP antibiotics: biosynthesis and engineering potential.

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New antibiotic discovery is crucial due to rising bacterial resistance. Ribosomally synthesized and post-translationally modified peptides (RiPPs) offer a promising avenue, with their adaptable biosynthetic pathways enabling the creation of novel drug compounds.

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Area of Science:

  • Microbiology
  • Biochemistry
  • Synthetic Biology

Background:

  • Antibiotic resistance necessitates novel therapeutic strategies.
  • Microbial natural products have historically yielded valuable antibiotics.
  • Limitations exist in engineering traditional antibiotic biosynthetic pathways.

Purpose of the Study:

  • To review ribosomally synthesized and post-translationally modified peptides (RiPPs) as a source of novel antibiotics.
  • To highlight the biosynthetic plasticity of RiPP pathways.
  • To explore the potential of RiPP engineering for new drug development.

Main Methods:

  • Review of prominent RiPPs with antibiotic activity.
  • Focus on the biosynthetic pathways and modular nature of RiPPs.
  • Discussion of synthetic biology approaches for RiPP engineering.

Main Results:

  • RiPPs are a rapidly expanding class of natural products with potent antibiotic activity.
  • RiPP biosynthetic pathways demonstrate inherent tolerance to alternative substrates.
  • Engineering RiPPs has already led to the generation of novel compounds.

Conclusions:

  • RiPPs represent a highly promising class of natural products for antibiotic development.
  • The biosynthetic plasticity of RiPPs is key to generating diverse analogs.
  • Synthetic biology offers powerful tools to unlock the full potential of RiPPs for combating antibiotic resistance.