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

Tingting Huang, Chin-Yuan Chang, Jeremy R. Lohman, Jeffrey D. Rudolf, Youngchang Kim, Changsoo Chang, Dong Yang, Ming Ma, Xiaohui Yan, Ivana Crnovcic, Lance Bigelow, Shonda Clancy, Craig A. Bingman, Ragothaman M. Yennamalli, Gyorgy Babnigg, Andrzej Joachimiak, George N. Phillips, Ben Shen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

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. These findings will help formulate hypotheses and design experiments to ascertain the function of SgcJ and its homologues in nine-membered enediyne core biosynthesis.

Original languageEnglish
Pages (from-to)731-740
Number of pages10
JournalJournal of Antibiotics
Volume69
Issue number10
DOIs
StatePublished - 1 Oct 2016

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