Issue 11, 2011

Diversity in natural product families is governed by more than enzyme promiscuity alone: establishing control of the pacidamycin portfolio

Abstract

As with many other antibiotics, pacidamycins are produced as a suite of related compounds. Unlike most other secondary metabolites, however, this diversity is not solely the result of the substrate promiscuity of the biosynthetic enzymes but also arises from a gene duplication event (Pac21, Pac21h) and control of the precursor pool (PhhA). We are demonstrating the ability to harness these three levels of control in order to direct the selective production of specific members of this family of metabolites in a “dial-a-molecule” fashion. Furthermore, PhhA is shown to be a phenylalanine 3-hydroxylase, the first of the iron- and tetrahydropterin-dependent aromatic amino acid hydroxylases to be characterised with this regioselectivity.

Graphical abstract: Diversity in natural product families is governed by more than enzyme promiscuity alone: establishing control of the pacidamycin portfolio

Supplementary files

Article information

Article type
Edge Article
Submitted
17 Jun 2011
Accepted
04 Jul 2011
First published
11 Aug 2011

Chem. Sci., 2011,2, 2182-2186

Diversity in natural product families is governed by more than enzyme promiscuity alone: establishing control of the pacidamycin portfolio

S. Grüschow, E. J. Rackham and R. J. M. Goss, Chem. Sci., 2011, 2, 2182 DOI: 10.1039/C1SC00378J

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