Scripps VIVO scripps research logo

  • Index
  • Log in
  • Home
  • People
  • Organizations
  • Research
  • Events
Search form

Functional characterization of tlmk unveiling unstable carbinolamide intermediates in the tallysomycin biosynthetic pathway

Academic Article
uri icon
  • Overview
  • Identity
  • Additional Document Info
  • View All
scroll to property group menus

Overview

authors

  • Wang, L. Y.
  • Tao, M. F.
  • Wendt-Pienkoski, E.
  • Galm, U.
  • Coughlin, J. M.
  • Shen, Ben

publication date

  • March 2009

journal

  • Journal of Biological Chemistry  Journal

abstract

  • Tallysomycins (TLMs) belong to the bleomycin family of anticancer antibiotics. TLMs differ from bleomycins primarily by the presence of a 4-amino-4,6-dideoxy-l-talose sugar attached to C-41 as part of a glycosylcarbinolamide. We previously proposed, on the basis of bioinformatics analysis of the tlm biosynthetic gene cluster from Streptoalloteichus hindustanus E465-94 ATCC 31158, that the tlmK gene is responsible for the attachment of this sugar moiety. We now report that inactivation of tlmK in S. hindustanus abolished TLM A and TLM B production, the resultant DeltatlmK mutant instead accumulated five new metabolites, and introduction of a functional copy of tlmK to the DeltatlmK mutant restored TLM A and TLM B production. Two major metabolites, TLM K-1 and TLM K-2, together with three minor metabolites, TLM K-3, TLM K-4, and TLM K-5, were isolated from the DeltatlmK mutant, and their structures were elucidated. These findings provide experimental evidence supporting the previous functional assignment of tlmK to encode a glycosyltransferase and unveil two carbinolamide pseudoaglycones as key intermediates in the TLM biosynthetic pathway. TlmK stabilizes the carbinolamide intermediates by glycosylating their hemiaminal hydroxyl groups, thereby protecting them from hydrolysis during TLM biosynthesis. In the absence of TlmK, the carbinolamide intermediates fragment to produce an amide TLM K-1 and aldehyde intermediates, which undergo further oxidative fragmentation to afford carboxylic acids TLM K-2, TLM K-3, TLM K-4, and TLM K-5.

subject areas

  • Actinomycetales
  • Antibiotics, Antineoplastic
  • Bacterial Proteins
  • Bleomycin
  • Gene Deletion
  • Genes, Bacterial
  • Glucosyltransferases
  • Multigene Family
scroll to property group menus

Identity

PubMed Central ID

  • PMC2659183

International Standard Serial Number (ISSN)

  • 0021-9258

Digital Object Identifier (DOI)

  • 10.1074/jbc.M900640200

PubMed ID

  • 19189972
scroll to property group menus

Additional Document Info

start page

  • 8256

end page

  • 8264

volume

  • 284

issue

  • 13

©2021 The Scripps Research Institute | Terms of Use | Powered by VIVO

  • About
  • Contact Us
  • Support