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. 2011 Jun 17;13(12):3048-51.
doi: 10.1021/ol200922s. Epub 2011 May 26.

Sources of diversity in bactobolin biosynthesis by Burkholderia thailandensis E264

Gavin Carr  1 , Mohammad R Seyedsayamdost, Josephine R Chandler, E Peter Greenberg, Jon Clardy
Affiliations
Free PMC article

Sources of diversity in bactobolin biosynthesis by Burkholderia thailandensis E264

Gavin Carr et al. Org Lett. .
Free PMC article

Abstract

A series of deletion mutants in the recently identified bactobolin biosynthetic pathway defined the roles of several key biosynthetic enzymes and showed how promiscuity in three enzyme systems allows this cluster to produce multiple products. Studies on the deletion mutants also led to four new bactobolin analogs that provide additional structure-activity relationships for this interesting antibiotic family.

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Figures

Figure 1
Figure 1
Structures of bactobolins A–H and actinobolin.
Figure 2
Figure 2
Bactobolin gene cluster and a proposed biosynthetic model. (A) Schematic of the bactobolin gene cluster. Genes involved in regulation (orange), metabolite/product transport (green), synthesis of OH-Cl2-Val (dark gray), synthesis of Ala-Ala (light gray), synthesis of the C6-polyketide and ensuing reactions (blue), tailoring reactions (red), and genes of unknown function (white) are detailed. The domain architectures for the PKS and NRPS genes are also shown. (B) Proposed bactobolin biosynthesis.(3c) See text for a description.
Figure 3
Figure 3
Metabolic profile of ΔBtaU B. thailandensis. (A) Ion-extracted HPLC-MS trace of partially purified culture supernatant from wt B. thailandensis (black trace for 1, gray trace for 3) and ΔBtaU B. thailandensis (brown trace for 1, orange trace for 3). (B) Putative reaction catalyzed by BtaU. (C) Proposed biosynthesis of OH-Cl2-Val based on the results herein. OH-Cl-Val is made in an analogous fashion, where BtaC adds a single Cl. The order of reactions by BtaC and BtaA is not known.
Figure 4
Figure 4
Inhibitory activity of 1, 3, and 7 against B. subtilis BS3610 (A) and E. coli K12 (B).
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