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Issue 11, 2011
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Diversity in natural product families is governed by more than enzyme promiscuity alone: establishing control of the pacidamycin portfolio

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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

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Publication details

The article was received on 17 Jun 2011, accepted on 04 Jul 2011 and first published on 11 Aug 2011


Article type: Edge Article
DOI: 10.1039/C1SC00378J
Citation: Chem. Sci., 2011,2, 2182-2186
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    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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