Chapter 9Non-Ribosomal Peptide Synthetases: Nature’s Indispensable Drug Factories

Richa Sharma, Ravi S. Manhas and Asha Chaubey*

Fermentation Technology Division, CSIR-Indian Institute of Integrative Medicine, Canal Road, Jammu, (India)

*Corresponding author: achaubey@iiim.ac.in

Abstract

The development of methods for rational drug design using non-ribosomal machinery called non-ribosomal peptide synthetases (NRPS) has emerged as an important area of research, as peptide natural products form the largest and diversified therapeutics. This may prove helpful to meet ever-increasing demand for the new antibiotics and therapeutics. Non-ribosomal peptides (NRPs) are a family of unique naturally produced secondary metabolites by microorganisms mainly bacteria i.e., Actinomycetes and Bacilli, fungi and marine organisms. NRPs are explicitly targeted in the frontier of the search for therapeutic agents and are naturally a promising pool of candidates. Approximately 5% of 205 grouped families of NRPs have become clinically approved drugs to treat emerging health threats. Recent breakthroughs in the structure, molecular mechanism and chemical biology underlying the A, C, T and TE domains within NRPS and their roles within NRPS assemblies have been extended to performing novel chemistry. This knowledge is crucial with regards to the potential to redesign NRPS-based biosynthetic pathways and tackle new and emerging challenges in human health for overcoming increasing antimicrobial resistance ...

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