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. 2013 Apr 5;15(7):1678-81.
doi: 10.1021/ol4004614. Epub 2013 Mar 22.

Mutasynthesis of fluorinated pactamycin analogues and their antimalarial activity

Khaled H Almabruk  1 , Wanli Lu, Yuexin Li, Mostafa Abugreen, Jane X Kelly, Taifo Mahmud
Affiliations

Mutasynthesis of fluorinated pactamycin analogues and their antimalarial activity

Khaled H Almabruk et al. Org Lett. .

Abstract

A mutasynthetic strategy has been used to generate fluorinated TM-025 and TM-026, two biosynthetically engineered pactamycin analogues produced by Streptomyces pactum ATCC 27456. The fluorinated compounds maintain excellent activity and selectivity toward chloroquine-sensitive and multidrug-resistant strains of malarial parasites as the parent compounds. The results also provide insights into the biosynthesis of 3-aminobenzoic acid in S. pactum.

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Figures

Figure 1
Figure 1
Identification of genes responsible for the production of pactamycin precursor.
Figure 2
Figure 2
HPLC analysis of EtOAc extracts of the wild-type and the mutant strains of S. pactum.
Figure 3
Figure 3
Mass spectral data for EtOAc (A – C) and n-BuOH (D – F) extracts of S. pactum mutants with and without chemical complementations.
Figure 4
Figure 4
Chemical structures of pactamycin analogs.
See this image and copyright information in PMC

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