Rational Domain Swaps Decipher Programming in Fungal Highly Reducing Polyketide Synthases and Resurrect an Extinct Metabolite

K.M Fisch, W.I.M Bakeer, A Yakasai, Z Song, J Pedrick, Z Wasil, A.M Bailey, C.M Lazarus, T.J Simpson, R.J Cox

Research output: Contribution to journalArticle (Academic Journal)peer-review

89 Citations (Scopus)

Abstract

The mechanism of programming of iterative highly reducing polyketide synthases remains one of the key unsolved problems of secondary metabolism. We conducted rational domain swaps between the polyketide synthases encoding the biosynthesis of the closely related compounds tenellin and desmethylbassianin. Expression of the hybrid synthetases in Aspergillus oryzae led to the production of reprogrammed compounds in which the changes to the methylation pattern and chain length could be mapped to the domain swaps. These experiments reveal for the first time the origin of programming in these systems. Domain swaps combined with coexpression of two cytochrome P450 encoding genes from the tenellin biosynthetic gene cluster led to the resurrection of the extinct metabolite bassianin.
Translated title of the contributionRational Domain Swaps Decipher Programming in Fungal Highly Reducing Polyketide Synthases and Resurrect an Extinct Metabolite
Original languageEnglish
Pages (from-to)16635 - 16641
Number of pages7
JournalJournal of the American Chemical Society
Volume133
Issue number41
DOIs
Publication statusPublished - Sep 2011

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