Heterologous biosynthesis of a fungal macrocyclic polylactone requires only two iterative polyketide synthases

Waraporn Bunnak, Passorn Wonnapinij, Ajaraporn Sriboonlert, Colin M Lazarus, Pakorn Wattana-Amorn

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

9 Citations (Scopus)


Menisporopsin A is a bioactive macrocyclic polylactone produced by the fungus Menisporopsis theobromae BCC 4162. A scheme for the biosynthesis of this compound has been proposed, in which reducing (R) and non-reducing (NR) polyketide synthases (PKSs) would catalyze the formation of each menisporopsin A subunit, while an additional non-ribosomal peptide synthetase (NRPS)-like enzyme would be required to perform multiple esterification and cyclolactonization reactions. Transcriptome analysis of M. theobromae identified an R-PKS gene, men1, and an NR-PKS gene, men2, which both exhibited highest expression levels during the menisporopsin A production phase. These were cloned into separate vectors for heterologous expression in Aspergillus oryzae NSAR1. Unexpectedly, coexpression of the two PKSs alone was sufficient to catalyze the formation of the macrocyclic polylactone, ascotrichalactone A, a structural derivative of menisporopsin A. The unanticipated esterification and cyclolactonization activities could reside in the unusual thioesterase domain of the NR-PKS, which is similar to that of the NRPS catalyzing elongation and cyclization of trilactone in enterobactin biosynthesis and that of modular PKSs catalyzing macrodiolide formation in elaiophylin and conglobatin biosyntheses.

Original languageEnglish
Pages (from-to)374-379
Number of pages6
JournalOrganic and Biomolecular Chemistry
Issue number2
Early online date11 Dec 2018
Publication statusPublished - 2 Jan 2019


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