Volume 18, Issue 11 p. 985-991
Communication

Head-to-Head Prenyl Synthases in Pathogenic Bacteria

Christopher J. Schwalen

Christopher J. Schwalen

Department of Chemistry, University of Illinois, 600 South Mathews Avenue, Urbana, IL, 61801 USA

These authors contributed equally to this work.

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Dr. Xinxin Feng

Dr. Xinxin Feng

Department of Chemistry, University of Illinois, 600 South Mathews Avenue, Urbana, IL, 61801 USA

These authors contributed equally to this work.

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Dr. Weidong Liu

Dr. Weidong Liu

Industrial Enzymes National Engineering Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, 32 West 7th Avenue, Tianjin, 300308 China

These authors contributed equally to this work.

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Bing O-Dowd

Bing O-Dowd

Department of Chemistry, University of Illinois, 600 South Mathews Avenue, Urbana, IL, 61801 USA

These authors contributed equally to this work.

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Dr. Tzu-Ping Ko

Dr. Tzu-Ping Ko

Institute of Biological Chemistry, Academia Sinica, 128 Academia Road Section 2, Taipei, 11529 Taiwan

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Christopher J. Shin

Christopher J. Shin

Department of Chemistry, University of Illinois, 600 South Mathews Avenue, Urbana, IL, 61801 USA

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Prof. Dr. Rey-Ting Guo

Prof. Dr. Rey-Ting Guo

Industrial Enzymes National Engineering Laboratory, Tianjin Institute of Industrial Biotechnology, Chinese Academy of Sciences, 32 West 7th Avenue, Tianjin, 300308 China

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Prof. Dr. Douglas A. Mitchell

Corresponding Author

Prof. Dr. Douglas A. Mitchell

Department of Chemistry, University of Illinois, 600 South Mathews Avenue, Urbana, IL, 61801 USA

Department of Microbiology, University of Illinois, 601 South Goodwin Avenue, Urbana, IL, 61801 USA

Carl R. Woese Institute for Genomic Biology, University of Illinois, 1206 West Gregory Drive, Urbana, IL, 61801 USA

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Prof. Dr. Dr. Eric Oldfield

Corresponding Author

Prof. Dr. Dr. Eric Oldfield

Department of Chemistry, University of Illinois, 600 South Mathews Avenue, Urbana, IL, 61801 USA

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First published: 24 March 2017
Citations: 6

Graphical Abstract

Putting their heads together: Bacteria that cause meningitis, gonorrhea and some cases of endocarditis and septicemia all express terpene synthase-like proteins. We showed that these head-to-head prenyl synthases generated presqualene diphosphate or dehydrosqualene and reported one X-ray structure with a bound inhibitor.

Abstract

Many organisms contain head-to-head isoprenoid synthases; we investigated three such types of enzymes from the pathogens Neisseria meningitidis, Neisseria gonorrhoeae, and Enterococcus hirae. The E. hirae enzyme was found to produce dehydrosqualene, and we solved an inhibitor-bound structure that revealed a fold similar to that of CrtM from Staphylococcus aureus. In contrast, the homologous proteins from Neisseria spp. carried out only the first half of the reaction, yielding presqualene diphosphate (PSPP). Based on product analyses, bioinformatics, and mutagenesis, we concluded that the Neisseria proteins were HpnDs (PSPP synthases). The differences in chemical reactivity to CrtM were due, at least in part, to the presence of a PSPP-stabilizing arginine in the HpnDs, decreasing the rate of dehydrosqualene biosynthesis. These results show that not only S. aureus but also other bacterial pathogens contain head-to-head prenyl synthases, although their biological functions remain to be elucidated.

Conflict of interest

The authors declare no conflict of interest.