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. 2011 Aug 31;133(34):13314-6.
doi: 10.1021/ja205780g. Epub 2011 Aug 10.

Engineering of an "unnatural" natural product by swapping polyketide synthase domains in Aspergillus nidulans

Ting Liu  1 , Yi-Ming Chiang, Amber D Somoza, Berl R Oakley, Clay C C Wang
Affiliations

Engineering of an "unnatural" natural product by swapping polyketide synthase domains in Aspergillus nidulans

Ting Liu et al. J Am Chem Soc. .

Abstract

An StcA-AfoE hybrid polyketide synthase (PKS), generated by swapping the AfoE (asperfuranone biosynthesis) SAT domain with the StcA (sterigmatocystin biosynthesis) SAT domian, produced a major new metabolite with the same chain length as the native AfoE product. Structure elucidation allowed us to propose a likely pathway, and feeding studies supported the hypothesis that the chain length of PKS metabolites may be under precise control of KS and PT domains.

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Figures

Figure 1
Figure 1
HPLC profiles of extracts of A. nidulans stcAΔ, hybrid B2 double mutant under noninducing (a) and inducing (b) conditions as detected by UV absorption at 254 nm. The y axis of each profile was at the same order of magnitude. *: metabolites that are nonspecific to this study.
Figure 2
Figure 2
Proposed biosynthetic pathway of asperfuranone and compound 1 from native AfoE (upper) and hybrid AfoE (lower).
Figure 3
Figure 3
(A) HPLC profiles of extracts of A. nidulans stcAΔ, hybrid B2, stcJΔstcKΔ triple mutant fed with DMSO (a), hexanoyl-SNAC (b) as detected by UV absorption at 254 nm. The y axis of each profile was at the same order of magnitude. (B) Summary of metabolites produced by hybrid AfoE based on feeding experiments. Each row lists the predicted ion formula, retention time (tR), m/z of unlabeled form, m/z of D11-incorperated form, and overall percentage of each metabolite in negative mode. *: assuming all molecules are equally ionizable in negative mode.
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