Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols

Marek Kõllo; Marje Kasari; Villu Kasari; Tõnis Pehk; Ivar Järving; Margus Lopp; Arvi Jõers; Tõnis Kanger

doi:10.3762/bjoc.17.52

Designed whole-cell-catalysis-assisted synthesis of 9,11-secosterols

Beilstein J Org Chem. 2021 Mar 1:17:581-588. doi: 10.3762/bjoc.17.52. eCollection 2021.

Authors

Marek Kõllo¹, Marje Kasari², Villu Kasari², Tõnis Pehk³, Ivar Järving¹, Margus Lopp¹, Arvi Jõers², Tõnis Kanger¹

Affiliations

¹ Department of Chemistry and Biotechnology, School of Science, Tallinn University of Technology, Akadeemia tee 15, 12618 Tallinn, Estonia.
² Institute of Technology, University of Tartu, Nooruse 1, 50104 Tartu, Estonia.
³ National Institute of Chemical Physics and Biophysics, Akadeemia tee 23, 12618 Tallinn, Estonia.

Abstract

A method for the synthesis of 9,11-secosteroids starting from the natural corticosteroid cortisol is described. There are two key steps in this approach, combining chemistry and synthetic biology. Stereo- and regioselective hydroxylation at C9 (steroid numbering) is carried out using whole-cell biocatalysis, followed by the chemical cleavage of the C-C bond of the vicinal diol. The two-step method features mild reaction conditions and completely excludes the use of toxic oxidants.

Keywords: chemoenzymatic synthesis; cortisol; hydroxylation; secosterol; whole-cell catalysis.

Grants and funding

The authors thank the Estonian Ministry of Education and Research (Grant Nos. PRG657 and PRG1031) and the Centre of Excellence in Molecular Cell Engineering (2014-2020.4.01.15-0013) for financial support.