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Structural Studies of Modular Nonribosomal Peptide Synthetases

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Non-Ribosomal Peptide Biosynthesis and Engineering

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2670))

Abstract

The non-ribosomal peptide synthetases (NRPSs) are a family of modular enzymes involved in the production of peptide natural products. Not restricted by the constraints of ribosomal peptide and protein production, the NRPSs are able to incorporate unusual amino acids and other suitable building blocks into the final product. The NRPSs operate with an assembly line strategy in which peptide intermediates are covalently tethered to a peptidyl carrier protein and transported to different catalytic domains for the multiple steps in the biosynthesis. Often the carrier and catalytic domains are joined into a single large multidomain protein. This chapter serves to introduce the NRPS enzymes, using the nocardicin NRPS system as an example that highlights many common features to NRPS biochemistry. We then describe recent advances in the structural biology of NRPSs focusing on large multidomain structures that have been determined.

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Acknowledgement

Work in our lab is supported with funding from the National Institutes of General Medical Sciences, NIH (GM-136235).

Conflict of Interest Statement

The authors declare no conflicts of interest with the contents of this article.

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Authors and Affiliations

  1. Department of Structural Biology, University at Buffalo, SUNY, Buffalo, NY, USA

    Ketan D. Patel, Syed Fardin Ahmed, Monica R. MacDonald & Andrew M. Gulick

  2. Department of Structural Biology, Jacobs School of Medicine & Biomedical Sciences, Buffalo, NY, USA

    Andrew M. Gulick

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  1. Ketan D. Patel
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  2. Syed Fardin Ahmed
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  3. Monica R. MacDonald
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  4. Andrew M. Gulick
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Corresponding author

Correspondence to Andrew M. Gulick .

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Editors and Affiliations

  1. Department of Chemistry and Biochemistry, University of California San Diego, La Jolla, CA, USA

    Michael Burkart

  2. Faculty of Pharmacy, Kindai University, Higashi-Osaka, Osaka, Japan

    Fumihiro Ishikawa

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Patel, K.D., Ahmed, S.F., MacDonald, M.R., Gulick, A.M. (2023). Structural Studies of Modular Nonribosomal Peptide Synthetases. In: Burkart, M., Ishikawa, F. (eds) Non-Ribosomal Peptide Biosynthesis and Engineering. Methods in Molecular Biology, vol 2670. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-3214-7_2

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  • DOI: https://doi.org/10.1007/978-1-0716-3214-7_2

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  • Publisher Name: Humana, New York, NY

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