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 article in proceedingsScientificpeer-review

1 Citation (Scopus)

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
Title of host publicationPolyketides Biosynthesis, Biological Activity, and Genetic Engineering
PublisherAmerican Chemical Society ACS
Pages217-230
Number of pages14
ISBN (Electronic)978-0-8412-2073-7
ISBN (Print)978-0-8412-3978-4
DOIs
Publication statusPublished - 2007
MoE publication typeA4 Article in a conference publication

Publication series

SeriesACS Symposium Series
Volume955
ISSN0097-6156

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