Simple “On‐Demand” Production of Bioactive Natural Products

Abstract

Exchange of the native promoter to the arabinose-inducible promoter PBAD was established in entomopathogenic bacteria to silence and/or activate gene clusters involved in natural product biosynthesis. This allowed the "on-demand" production of GameXPeptides, xenoamicins, and the blue pigment indigoidine. The gene clusters for the novel "mevalagmapeptides" and the highly toxic xenorhabdins were identified by this approach.

Screening of the Antimicrobial Activity against Drug Resistant Bacteria of Photorhabdus and Xenorhabdus Associated with Entomopathogenic Nematodes from Mae Wong National Park, Thailand

“…All Xenorhabdus isolates produced xenoamicin derivatives showing weak antiprotozoal activity (Zhou et al, 2013). Additionally, we identified mevalagmapeptide (Bode et al, 2015, 2012) and the juvenile hormone epoxide hydrolase inhibitors phurealipids (Nollmann et al, 2015b) in many of the isolates.…”

Predominately Uncultured Microbes as Sources of Bioactive Agents

“…These include, but are not limited to: discussion of eliciting secondary metabolism in actinomycetes (Seyedsayamdost et al, 2012; Abdelmohsen et al, 2015; Rutledge and Challis, 2015); methodologies for determining the compounds expressed (Adnani et al, 2014; Luzzatto-Knaan et al, 2015; Medema and Fischbach, 2015; Mohimani and Pevzner, 2016); analyses of the biosynthetic clusters identified in fungi to published natural product structures (Li et al, 2016b); small-scale plate-based techniques for fungal co-culture (Bertrand et al, 2014); on-demand production of secondary metabolites (Bode et al, 2015); mixed culture of endophytes (Chagas et al, 2013); metabolomics in induced cultures (Derewacz et al, 2015; van der Lee and Medema, 2016; Zhang et al, 2016a,b; Ziemert et al, 2016); use of synthetic biological techniques to further expand the chemical biodiversity discovered (Smanski et al, 2016); and a recent review of the array of approaches to study such cryptic cluster expression by Zarins-Tutt et al (2016).…”

Structure, Biosynthesis, and Occurrence of Bacterial Pyrrolizidine Alkaloids

“…In Streptomyces Mg1 and N. cyriacigeorgica,P xaB is fused to an NRPS-like condensation domain that is most similar to standard elongation domains ( Figure S12), and in legonmycin biosynthesis,t he PxaA homologue is split into two enzymes. [20] No PA gene cluster has been linked to the production of such compounds in any of the identified strains except for MA37 [20] despite the fact that some of them have been well studied, such as P. aeruginosa or S. clavuligerus.T herefore, apromoter exchange approach [21] was used to activate the PA gene cluster in the genetically accessible X. szentirmaii,which resulted in the production of pyrrolizixenamide D( 8;F igure S13), differing from 1 in the presence of ab ranched acyl moiety ( Figure S5). …”