Format

Send to

Choose Destination
Sci Rep. 2018 Feb 23;8(1):3538. doi: 10.1038/s41598-018-21887-9.

Directed evolution of SIRT6 for improved deacylation and glucose homeostasis maintenance.

Author information

1
Department of Life Sciences, Ben-Gurion University of the Negev, Be'er Sheva, 84105, Israel.
2
Smartzyme Innovation LTD, Ilan Ramon, Science Park-Ness Ziona, Ness Ziona, Israel.
3
The Mina & Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 5290002, Israel.
4
Department of Life Sciences, Ben-Gurion University of the Negev, Be'er Sheva, 84105, Israel. aaharoni@bgu.ac.il.
5
The National Institute for Biotechnology in the Negev, Ben-Gurion University of the Negev, Be'er Sheva, 84105, Israel. aaharoni@bgu.ac.il.

Abstract

Mammalian SIRT6 is a well-studied histone deacetylase that was recently shown to exhibit high protein deacylation activity enabling the removal of long chain fatty acyl groups from proteins. SIRT6 was shown to play key roles in cellular homeostasis by regulating a variety of cellular processes including DNA repair and glucose metabolism. However, the link between SIRT6 enzymatic activities and its cellular functions is not clear. Here, we utilized a directed enzyme evolution approach to generate SIRT6 mutants with improved deacylation activity. We found that while two mutants show increased deacylation activity at high substrate concentration and improved glucose metabolism they exhibit no improvement and even abolished deacetylation activity on H3K9Ac and H3K56Ac in cells. Our results demonstrate the separation of function between SIRT6 catalytic activities and suggest that SIRT6 deacylation activity in cells is important for glucose metabolism and can be mediated by still unknown acylated cellular proteins.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center