Enediyne biosynthesis and self-resistance: A progress report Journal Article


Authors: Thorson, J. S.; Shen, B.; Whitwam, R. E.; Liu, W.; Li, Y.; Ahlert, J.
Article Title: Enediyne biosynthesis and self-resistance: A progress report
Abstract: The enediyne antitumor antibiotics are appreciated for their novel molecular architecture, remarkable biological activity, and fascinating mode of action, and many have spawned considerable interest as anticancer agents in the pharmaceutical industry. Of equal importance to these astonishing properties, the enediynes also offer a distinct opportunity to study the unparalleled biosyntheses of their unique molecular scaffolds and what promises to be unprecedented modes of self-resistance to highly reactive natural products. Elucidation of these aspects should unveil novel mechanistic enzymology and may provide access to the rational biosynthetic modification of enediyne structure for new drug leads, the construction of enediyne overproducing strains, and eventually lead to an enediyne combinatorial biosynthesis program. This article reviews the published enediyne biosynthetic labeling and blocked mutant studies and provides a brief account of efforts in the Shen laboratory to elucidate the route to C- 1027 biosynthesis and efforts in the Thorson laboratory to elucidate the calicheamicin biosynthetic cascade.
Keywords: gene cluster; nonhuman; conference paper; drug structure; enzymology; molecular cloning; antibiotic resistance; amino acid sequence; drug mechanism; laboratory; natural product; antineoplastic antibiotic; enzyme mechanism; streptomyces; bicyclo compound; actinomyces; fungus mutant; calicheamicin; polyketide; priority journal; xanthine derivative; antibiotic biosynthesis; antibiotic c 1027; micromonospora; apoprotein; auromomycin; dynemicin a; esperamicin derivative; kedarcidin; maduramicin; zinostatin
Journal Title: Bioorganic Chemistry
Volume: 27
Issue: 2
ISSN: 0045-2068
Publisher: Academic Press Inc., Elsevier Science  
Date Published: 1999-04-01
Start Page: 172
End Page: 188
Language: English
DOI: 10.1006/bioo.1998.1122
PROVIDER: scopus
DOI/URL:
Notes: Conference Paper -- Export Date: 16 August 2016 -- Source: Scopus
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  1. Jon S Thorson
    22 Thorson
  2. Joachim   Ahlert
    6 Ahlert