Isonitrile Formation by a Non-Heme Iron(II)-Dependent Oxidase/Decarboxylase

Nicholas C Harris; David A Born; Wenlong Cai; Yaobing Huang; Joelle Martin; Ryan Khalaf; Catherine L Drennan; Wenjun Zhang

doi:10.1002/anie.201804307

Isonitrile Formation by a Non-Heme Iron(II)-Dependent Oxidase/Decarboxylase

Angew Chem Int Ed Engl. 2018 Jul 26;57(31):9707-9710. doi: 10.1002/anie.201804307. Epub 2018 Jul 3.

Authors

Nicholas C Harris¹, David A Born^{2

3}, Wenlong Cai⁴, Yaobing Huang⁴, Joelle Martin⁵, Ryan Khalaf⁵, Catherine L Drennan^{2

6

7}, Wenjun Zhang^{4

8}

Affiliations

¹ Department of Plant and Microbial Biology, University of California Berkeley, Berkeley, CA, 94720, USA.
² Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
³ Graduate Program in Biophysics, Harvard University, Cambridge, MA, 02138, USA.
⁴ Department of Chemical and Biomolecular Engineering, University of California Berkeley, Berkeley, CA, 94720, USA.
⁵ Department of Chemistry, University of California Berkeley, Berkeley, CA, 94720, USA.
⁶ Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
⁷ Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.
⁸ Chan Zuckerberg Biohub, San Francisco, CA, 94158, USA.

Abstract

The electron-rich isonitrile is an important functionality in bioactive natural products, but its biosynthesis has been restricted to the IsnA family of isonitrile synthases. We herein provide the first structural and biochemical evidence of an alternative mechanism for isonitrile formation. ScoE, a putative non-heme iron(II)-dependent enzyme from Streptomyces coeruleorubidus, was shown to catalyze the conversion of (R)-3-((carboxymethyl)amino)butanoic acid to (R)-3-isocyanobutanoic acid through an oxidative decarboxylation mechanism. This work further provides a revised scheme for the biosynthesis of a unique class of isonitrile lipopeptides, of which several members are critical for the virulence of pathogenic mycobacteria.

Keywords: acyl-acyl carrier protein ligase; biosynthesis; isocyanide; oxidoreductase; protein structures.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Biocatalysis
Carboxy-Lyases / chemistry
Carboxy-Lyases / metabolism*
Ferrous Compounds / chemistry
Ferrous Compounds / metabolism*
Models, Molecular
Molecular Structure
Nitriles / chemistry
Nitriles / metabolism*
Oxidoreductases / chemistry
Oxidoreductases / metabolism*
Streptomyces / enzymology

Substances

Ferrous Compounds
Nitriles
Oxidoreductases
Carboxy-Lyases

Abstract

Publication types

MeSH terms

Substances

Grants and funding