Biosynthesis of the antifungal polyketide antibiotic soraphen A in Sorangium cellulosum and Streptomyces lividans

István Molnár, Ross Zirkle, James M. Ligón

Research output: Chapter in Book/Report/Conference proceedingConference contribution

1 Scopus citations

Abstract

The derivatization of soraphen by combinatorial biosynthesis has been a longstanding goal of the Natural Product Genetics group at Ciba Geigy - Novartis - Syngenta. We have cloned and characterized the soraphen A biosynthetic gene cluster of Sorangium cellulosum So ce26. To facilitate the genetic manipulation of So ce26, a central regulator of gliding motility was identified and its encoding gene disrupted to create a nonswarming strain. Despite this improvement, engineering of soraphen biosynthesis remained elusive in So ce26. Thus, the genes for the soraphen polyketide synthase, the post-polyketide tailoring steps, and methoxymalonate biosynthesis were introduced into Streptomyces lividans. Production of soraphen A in this genetically tractable strain also required provision of benzoyl-CoA by feeding benzoate or cinnamate.

Original languageEnglish (US)
Title of host publicationPolyketides Biosynthesis, Biological Activity, and Genetic Engineering
PublisherAmerican Chemical Society
Pages217-230
Number of pages14
ISBN (Print)0841239789, 9780841239784
DOIs
StatePublished - Jan 1 2007

Publication series

NameACS Symposium Series
Volume955
ISSN (Print)0097-6156

ASJC Scopus subject areas

  • Chemistry(all)
  • Chemical Engineering(all)

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    Molnár, I., Zirkle, R., & Ligón, J. M. (2007). Biosynthesis of the antifungal polyketide antibiotic soraphen A in Sorangium cellulosum and Streptomyces lividans. In Polyketides Biosynthesis, Biological Activity, and Genetic Engineering (pp. 217-230). (ACS Symposium Series; Vol. 955). American Chemical Society. https://doi.org/10.1021/bk-2007-0955.ch015