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Crystal structure of SgcJ, an NTF2-like superfamily protein involved in biosynthesis of the nine-membered enediyne antitumor antibiotic C-1027

Journal Article · · The Journal of Antibiotics
DOI:https://doi.org/10.1038/ja.2016.88· OSTI ID:1374053
 [1];  [2];  [3];  [2];  [4];  [5];  [2];  [2];  [2];  [2];  [5];  [5];  [6];  [7];  [4];  [4];  [8];  [2]
  1. The Scripps Research Institute, Jupiter, FL (United States); Shanghai Jiao Tong Univ., Shanghai (China)
  2. The Scripps Research Institute, Jupiter, FL (United States)
  3. The Scripps Research Institute, Jupiter, FL (United States); Purdue Univ., West Lafayette, IN (United States)
  4. Univ. of Chicago, Chicago, IL (United States); Argonne National Lab. (ANL), Argonne, IL (United States)
  5. Argonne National Lab. (ANL), Argonne, IL (United States)
  6. Univ. of Wisconsin, Madison, WI (United States)
  7. Rice Univ., Houston, TX (United States); Jaypee Univ. of Information Technology, Himachal Pradesh (India)
  8. Rice Univ., Houston, TX (United States)
+ Show Author Affiliations

Comparative analysis of the enediyne biosynthetic gene clusters revealed sets of conserved genes serving as outstanding candidates for the enediyne core. Here we report the crystal structures of SgcJ and its homologue NCS-Orf16, together with gene inactivation and site-directed mutagenesis studies, to gain insight into enediyne core biosynthesis. Gene inactivation in vivo establishes that SgcJ is required for C-1027 production in Streptomyces globisporus. SgcJ and NCS-Orf16 share a common structure with the nuclear transport factor 2-like superfamily of proteins, featuring a putative substrate binding or catalytic active site. Site-directed mutagenesis of the conserved residues lining this site allowed us to propose that SgcJ and its homologues may play a catalytic role in transforming the linear polyene intermediate, along with other enediyne polyketide synthase-associated enzymes, into an enzyme-sequestered enediyne core intermediate. In conclusion, these findings will help formulate hypotheses and design experiments to ascertain the function of SgcJ and its homologues in nine-membered enediyne core biosynthesis.

Research Organization:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Organization:
Scripps Research Institute; German Research Foundation (DFG); National Institutes of Health (NIH), National Institute of General Medical Sciences; USDOE Office of Science (SC), Biological and Environmental Research (BER) (SC-23)
Grant/Contract Number:
AC02-06CH11357
OSTI ID:
1374053
Journal Information:
The Journal of Antibiotics, Journal Name: The Journal of Antibiotics Journal Issue: 10 Vol. 69; ISSN 0021-8820
Publisher:
Nature Publishing GroupCopyright Statement
Country of Publication:
United States
Language:
English

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