Issue 7, 2019

Synthesis of N-acyl amide natural products using a versatile adenylating biocatalyst

Abstract

Natural products are secondary metabolites produced by many different organisms such as bacteria, fungi and plants. These biologically active molecules have been widely exploited for clinical application. Here we investigate TamA, a key enzyme from the biosynthetic pathway of tambjamine YP1, an acylated bipyrrole that is produced by the marine microorganism Pseudoalteromonas tunicata. TamA is a didomain enzyme composed of a catalytic adenylation (ANL) and an acyl carrier protein (ACP) domain that together control the fatty acid chain length of the YP1. Here we show that the TamA ANL domain alone can be used to generate a range of acyl adenylates that can be captured by a number of amines thus leading to the production of a series of fatty N-acyl amides. We exploit this biocatalytic promiscuity to produce the recently discovered class of N-acyl histidine amide natural products from Legionella pneumophila.

Graphical abstract: Synthesis of N-acyl amide natural products using a versatile adenylating biocatalyst

Supplementary files

Article information

Article type
Research Article
Submitted
01 Feb 2019
Accepted
22 May 2019
First published
31 May 2019
This article is Open Access
Creative Commons BY-NC license

Med. Chem. Commun., 2019,10, 1192-1196

Synthesis of N-acyl amide natural products using a versatile adenylating biocatalyst

P. M. Marchetti, S. M. Richardson, N. M. Kariem and D. J. Campopiano, Med. Chem. Commun., 2019, 10, 1192 DOI: 10.1039/C9MD00063A

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Spotlight

Advertisements