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

Sabine Grüschow ; Emma J. Rackham ; Rebecca J. M. Goss Chem Sci 2011, 2 2182-2186 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, … Read more

Pacidamycin Biosynthesis : Identification and Heterologous Expression of the First Uridyl Peptide Antibiotic Gene Cluster

Emma J. Rackham ; Sabine Grüschow ; Amany E. Ragab ; Shilo Dickens ; Rebecca J. M. Goss ChemBioChem 2010, 11 (12) 1700-1709 The pacidamycins are antimicrobial nucleoside antibiotics produced by Streptomyces coeruleorubidus that inhibit translocase I, an essential bacterial enzyme yet to be clinically targeted. The novel pacidamycin scaffold is composed of a pseudopeptide backbone linked by … Read more

New pacidamycins biosynthetically: probing N- and C-terminal substrate specificity

Amany E. Ragab ; Sabine Grüschow ; Emma J. Rackham ; Rebecca J. M. Goss Org Biomol Chem 2010, 8 3128-3129 Feeding phenylalanine analogues to Streptomyces coeruleorubidus reveals the remarkable steric and electronic flexibility of this biosynthetic pathway and leads to the generation of a series of new halopacidamycins.

New Pacidamycin Antibiotics Through Precursor-Directed Biosynthesis

Sabine Gruschow ; Emma J. Rackham ; Benjamin Elkins ; Philip L. A. Newilll ; Lionel M. Hill ; Rebecca J. M. Goss ChemBioChem 2009, 10 (2) 355-360 Pacidamycins, mureidomycins and napsamycins are structurally related uridyl peptide antibiotics that inhibit translocase I, an as yet clinically unexploited target. This potentially important bioactivity coupled to the biosynthetically intriguing … Read more