Synthetic-bioinformatic natural product-inspired peptides

Area of Science:

• Biochemistry
• Bioinformatics
• Natural Product Discovery

Background:

• Natural products, especially cyclic peptides, are vital sources of bioactive compounds.
• Nonribosomal peptide synthetases (NRPSs) are key enzymes in synthesizing these compounds, including antibiotics and anticancer agents.
• Traditional natural product discovery faces challenges like cryptic biosynthetic gene clusters (BGCs) and unculturable organisms.

Purpose of the Study:

• To explore alternative approaches for natural product discovery.
• To highlight the potential of synthetic-bioinformatic natural products (syn-BNPs).
• To review the successes and challenges of the syn-BNP approach.

Main Methods:

• Utilizing bioinformatics to predict nonribosomal peptides (NRPs).
• Chemical synthesis of predicted NRPs.
• Reviewing literature on syn-BNP discoveries and applications.

Main Results:

• The syn-BNP approach has successfully identified various bioactive compounds.
• Discovered peptides exhibit antibacterial, antifungal, anticancer, and proteasome-stimulating activities.
• This method enables access to peptides from previously inaccessible sources.

Conclusions:

• Synthetic-bioinformatic natural products offer a promising alternative to traditional discovery methods.
• Challenges remain in predicting modifications like fatty acid incorporation and enzyme tailoring.
• Further advancements are needed to fully unlock the potential of syn-BNPs for drug discovery.