Abstract

We report the draft genome sequence of Actinokineospora bangkokensis 44EHWT, the producer of the antifungal polyene compounds, thailandins A and B. The sequence contains 7.45 Mb, 74.1% GC content and 35 putative gene clusters for the biosynthesis of secondary metabolites. There are three gene clusters encoding large polyketide synthases of type I. Annotation of the ORF functions and targeted gene disruption enabled us to identify the cluster for thailandin biosynthesis. We propose a plausible biosynthetic pathway for thailandin, where the unusual butylmalonyl-CoA extender unit is incorporated and results in an untypical side chain.

Highlights

  • Generation sequencing and genome mining are powerful and rapid technologies to identify the genetic potential of a strain to synthesize secondary metabolites with various biological activities

  • Thailandin B is probably the precursor of the A-form, because thailandin A is further rhamnosylated. Both compounds show activity against pathogenic fungal strains with minimum inhibitory3.concentrations ranging between 16–32 μg/mL [8]

  • T produces the polyene thailandin and plasma bangkokensis membranethailandin by interacting withB isthe mainthesterol, ergosterol, which results in membrane

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Summary

Introduction

Generation sequencing and genome mining are powerful and rapid technologies to identify the genetic potential of a strain to synthesize secondary metabolites with various biological activities. One order known to produce many secondary metabolites with different bioactivities is the Actinomycetales. Under laboratory conditions only a few compounds are produced by a strain while their genomes comprise often more than 20 biosynthetic gene clusters. Cryptic clusters have been activated by heterologous expression [1], changing growth conditions [2] or by the manipulation of regulatory genes [3,4]. The knowledge of the genome sequence and the biosynthetic cluster composition of a secondary metabolite gives insights into the biosynthetic pathway. It is a valuable tool for metabolic engineering to increase the production of a specific compound or to generate novel metabolites by combinatorial biosynthesis

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