Applied Microbiology and Biotechnology

, Volume 97, Issue 18, pp 8183–8191

Mutasynthesis of pyrrole spiroketal compound using calcimycin 3-hydroxy anthranilic acid biosynthetic mutant

Applied genetics and molecular biotechnology

Abstract

The five-membered aromatic nitrogen heterocyclic pyrrole ring is a building block for a wide variety of natural products. Aiming at generating new pyrrole-containing derivatives as well as to identify new candidates that may be of value in designing new anticancer, antiviral, and/or antimicrobial agents, we employed a strategy on pyrrole-containing compound mutasynthesis using the pyrrole-containing calcimycin biosynthetic gene cluster. We blocked the biosynthesis of the calcimycin precursor, 3-hydroxy anthranilic acid, by deletion of calB1-3 and found that two intermediates containing the pyrrole and the spiroketal moiety were accumulated in the culture. We then fed the mutant using the structurally similar compound of 3-hydroxy anthranilic acid. At least four additional new pyrrole spiroketal derivatives were obtained. The structures of the intermediates and the new pyrrole spiroketal derivatives were identified using LC-MS and NMR. One of them shows enhanced antibacterial activity. Our work shows a new way of pyrrole derivative biosynthetic mutasynthesis.

Keywords

Calcimycin Pyrrole Mutasynthesis 3-Hydroxy anthranilic acid 

Supplementary material

253_2013_4882_MOESM1_ESM.pdf (500 kb)
ESM 1(PDF 500 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  1. 1.State Key Laboratory of Crop Stress Biology for Arid Areas and College of Plant ProtectionNorthwest A&F UniversityYanglingChina
  2. 2.State Key Laboratory of Microbial Metabolism, School of Life Science & BiotechnologyShanghai Jiaotong UniversityShanghaiChina
  3. 3.School of Traditional Chinese Materia MedicaShenyang Pharmaceutical UniversityShenyangPeople’s Republic of China

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