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Medium optimization of Streptomyces sp. 17944 for tirandamycin B production and isolation and structural elucidation of tirandamycins H, I and J. J Antibiot (Tokyo) 2014 Jan;67(1):127-32

Date

05/30/2013

Pubmed ID

23715040

Pubmed Central ID

PMC3773001

DOI

10.1038/ja.2013.50

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.

Author List

Rateb ME, Yu Z, Yan Y, Yang D, Huang T, Vodanovic-Jankovic S, Kron MA, Shen B

Author

Michael Kron MD Director, Professor in the Medicine department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Aminoglycosides
Culture Media
Drug Design
Fermentation
Filaricides
Streptomyces
Structure-Activity Relationship
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