5f8b

Structural highlights

Function

PSOE_ASPFU Glutathione S-transferase; part of the gene cluster that mediates the biosynthesis of pseurotin A, a competitive inhibitor of chitin synthase and an inducer of nerve-cell proliferation (PubMed:24082142, PubMed:24939566). The PKS-NRPS hybrid synthetase psoA is responsible for the biosynthesis of azaspirene, one of the first intermediates having the 1-oxa-7-azaspiro[4,4]-non-2-ene-4,6-dione core of pseurotin, via condensation of one acetyl-CoA, 4 malonyl-CoA, and a L-phenylalanine molecule (PubMed:24082142, PubMed:24939566). The dual-functional monooxygenase/methyltransferase psoF seems to be involved in the addition of the C3 methyl group onto the pseurotin scaffold (PubMed:24939566). Azaspirene is then converted to synerazol through 4 steps including oxidation of C17 by the cytochrome P450 monooxygenase psoD, O-methylation of the hydroxy group of C8 by the methyltransferase psoC, and the trans-to-cis isomerization of the C13 olefin by the glutathione S-transferase psoE (PubMed:24939566, PubMed:27072782). The fourth step of synerazol production is performed by the dual-functional monooxygenase/methyltransferase psoF which seems to catalyze the epoxidation of the intermediate deepoxy-synerazol (PubMed:24939566). Synerazol can be attacked by a water molecule nonenzymatically at two different positions to yield two diol products, pseurotin A and pseurotin D (PubMed:24939566).^{[1] [2] [3]}

References

1. ↑ Wiemann P, Guo CJ, Palmer JM, Sekonyela R, Wang CC, Keller NP. Prototype of an intertwined secondary-metabolite supercluster. Proc Natl Acad Sci U S A. 2013 Oct 15;110(42):17065-70. doi:, 10.1073/pnas.1313258110. Epub 2013 Sep 30. PMID:24082142 doi:http://dx.doi.org/10.1073/pnas.1313258110
2. ↑ Tsunematsu Y, Fukutomi M, Saruwatari T, Noguchi H, Hotta K, Tang Y, Watanabe K. Elucidation of pseurotin biosynthetic pathway points to trans-acting C-methyltransferase: generation of chemical diversity. Angew Chem Int Ed Engl. 2014 Aug 4;53(32):8475-9. doi: 10.1002/anie.201404804., Epub 2014 Jun 18. PMID:24939566 doi:http://dx.doi.org/10.1002/anie.201404804
3. ↑ Yamamoto T, Tsunematsu Y, Hara K, Suzuki T, Kishimoto S, Kawagishi H, Noguchi H, Hashimoto H, Tang Y, Hotta K, Watanabe K. Oxidative trans to cis Isomerization of Olefins in Polyketide Biosynthesis. Angew Chem Int Ed Engl. 2016 May 17;55(21):6207-10. doi: 10.1002/anie.201600940. , Epub 2016 Apr 13. PMID:27072782 doi:http://dx.doi.org/10.1002/anie.201600940