Medium optimization of streptomyces sp. 17944 for tirandamycin B production and isolation and structural elucidation of tirandamycins H, I and J

Mostafa E. Rateb, Zhiguo Yu, Yijun Yan, Dong Yang, Tingting Huang, Sanja Vodanovic-Jankovic, Michael A. Kron, Ben Shen

Research output: Contribution to journalArticlepeer-review

22 Citations (Scopus)

Abstract

We have recently isolated tirandamycin (TAM) B from Streptomyces sp. 17944 as a Brugia malayi AsnRS (BmAsnRS) inhibitor that efficiently kills the adult B. malayi parasites and does not exhibit general cytotoxicity to human hepatic cells. We now report (i) the comparison of metabolite profiles of S. sp. 17944 in six different media, (ii) identification of a medium enabling the production of TAM B as essentially the sole metabolite, and with improved titer, and (iii) isolation and structural elucidation of three new TAM congeners. These findings shed new insights into the structure–activity relationship of TAM B as a BmAsnRS inhibitor, highlighting the δ-hydroxymethyl-α,β-epoxyketone moiety as the critical pharmacophore, and should greatly facilitate the production and isolation of sufficient quantities of TAM B for further mechanistic and preclinical studies to advance the candidacy of TAM B as an antifilarial drug lead. The current study also serves as an excellent reminder that traditional medium and fermentation optimization should continue to be very effective in improving metabolite flux and titer.
Original languageEnglish
Pages (from-to)127-132
Number of pages6
JournalThe Journal of Antibiotics
Volume67
DOIs
Publication statusPublished - 29 May 2013
Externally publishedYes

Keywords

  • AsnRS inhibitor
  • filariasis
  • medium optimization
  • S. sp 17944
  • tirandamycin

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