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fabC of Streptomyces lydicus involvement in the biosynthesis of streptolydigin

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Streptolydigin, a secondary metabolite produced by Streptomyces lydicus, is a potent inhibitor of bacterial RNA polymerases. It has been suggested that streptolydigin biosynthesis is associated with polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS). Thus, there is great interest in understanding the role of fatty acid biosynthesis in the biosynthesis of streptolydigin. In this paper, we cloned a type II fatty acid synthase (FAS II) gene cluster of fabDHCF from the genome of S. lydicus and constructed the SlyfabCF-disrupted mutant. Sequence analysis showed that SlyfabDHCF is 3.7 kb in length and encodes four separated proteins with conserved motifs and active residues, as shown in the FAS II of other bacteria. The SlyfabCF disruption inhibited streptolydigin biosynthesis and retarded mycelial growth, which were likely caused by the inhibition of fatty acid synthesis. Streptolydigin was not detected in the culture of the mutant strain by liquid chromatography–mass spectrometry. Meanwhile, the streptolol moiety of streptolydigin accumulated in cultures. As encoded by fabCF, acyl carrier protein (ACP) and β-ketoacyl-ACP synthase II are required for streptolydigin biosynthesis and likely involved in the step between PKS and NRPS. Our results provide the first genetic and metabolic evidence that SlyfabCF is shared by fatty acid synthesis and antibiotic streptolydigin synthesis.

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This study was supported by the National Basic Research Program of China (2007CB714301), the National Natural Science Foundation of China (20736006), the National Fund for Distinguished Young Scholars (20425620), Key Projects in the National Science and Technology Pillar Program (no. 2007BAD42B02), the Natural Science Foundation of Tianjin (06YFJMC07300), and the Program of Introducing Talents of Discipline to Universities (no. B6006).

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Correspondence to Guang-Rong Zhao.

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Zhao, G., Luo, T., Zhou, Y. et al. fabC of Streptomyces lydicus involvement in the biosynthesis of streptolydigin. Appl Microbiol Biotechnol 83, 305–313 (2009). https://doi.org/10.1007/s00253-009-1872-4

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  • Streptolydigin
  • Fatty acid biosynthetic gene cluster
  • Metabolism
  • Acyl carrier protein
  • Streptomyces lydicus
  • Polyketide