alexa The genomisotopic approach: a systematic method to isolate products of orphan biosynthetic gene clusters.
Biochemistry

Biochemistry

Biochemistry & Analytical Biochemistry

Author(s): Gross H, Stockwell VO, Henkels MD, NowakThompson B, Loper JE,

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Abstract With the increasing number of genomes sequenced and available in the public domain, a large number of orphan gene clusters, for which the encoded natural product is unknown, have been identified. These orphan gene clusters represent a tremendous source of novel and possibly bioactive compounds. Here, we describe a "genomisotopic approach," which employs a combination of genomic sequence analysis and isotope-guided fractionation to identify unknown compounds synthesized from orphan gene clusters containing nonribosomal peptide synthetases. Analysis of the Pseudomonas fluorescens Pf-5 genome led to the identification of an orphan gene cluster predicted to code for the biosynthesis of a lipopeptide natural product. Application of the genomisotopic approach to isolate the product of this gene cluster resulted in the discovery of orfamide A, founder of a group of bioactive cyclic lipopeptides. This article was published in Chem Biol and referenced in Biochemistry & Analytical Biochemistry

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