Novel terpenes generated by heterologous expression of bacterial terpene synthase genes in an engineered Streptomyces host

Yuuki Yamada; Shiho Arima; Tohru Nagamitsu; Kohei Johmoto; Hidehiro Uekusa; Tadashi Eguchi; Kazuo Shin-ya; David E Cane; Haruo Ikeda

doi:10.1038/ja.2014.171

Novel terpenes generated by heterologous expression of bacterial terpene synthase genes in an engineered Streptomyces host

J Antibiot (Tokyo). 2015 Jun;68(6):385-94. doi: 10.1038/ja.2014.171. Epub 2015 Jan 21.

Authors

Yuuki Yamada¹, Shiho Arima², Tohru Nagamitsu², Kohei Johmoto³, Hidehiro Uekusa³, Tadashi Eguchi³, Kazuo Shin-ya⁴, David E Cane⁵, Haruo Ikeda¹

Affiliations

¹ Kitasato Institute for Life Sciences, Kitasato University, Kitasato, Sagamihara, Kanagawa, Japan.
² School of Pharmacy, Kitasato University, Shirokane, Minato-ku, Tokyo, Japan.
³ Department of Chemistry and Materials Science, Tokyo Institute of Technology, O-okayama, Meguro-ku, Tokyo, Japan.
⁴ National Institute of Advanced Industrial Science and Technology, Aomi, Koto-ku, Tokyo, Japan.
⁵ Department of Chemistry, Box H, Brown University, Providence, RI, USA.

Abstract

Mining of bacterial genome data has revealed numerous presumptive terpene synthases. Heterologous expression of several putative terpene synthase genes in an engineered Streptomyces host has revealed 13 newly discovered terpenes whose GC-MS and NMR data did not match with any known compounds in spectroscopic databases. Each of the genes encoding the corresponding terpene synthases were silent in their parent microorganisms. Heterologous expression and detailed NMR spectroscopic analysis allowed assignment of the structures of 13 new cyclic terpenes. Among these newly identified compounds, two were found to be linear triquinane sesquiterpenes that have never previously been isolated from bacteria or any other source. The remaining 11 new compounds were shown to be diterpene hydrocarbons and alcohol, including hydropyrene (1), hydropyrenol (2), tsukubadiene (11) and odyverdienes A (12) and B (13) each displaying a novel diterpene skeleton that had not previously been reported.

Publication types

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

MeSH terms

Actinomycetales / enzymology*
Actinomycetales / genetics
Actinomycetales / metabolism
Alkyl and Aryl Transferases / genetics
Alkyl and Aryl Transferases / metabolism*
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / isolation & purification
Anti-Bacterial Agents / metabolism
Bacterial Proteins / genetics
Bacterial Proteins / metabolism*
Chemical Phenomena
Crystallography, X-Ray
Databases, Chemical
Diterpenes / chemistry
Diterpenes / isolation & purification
Diterpenes / metabolism
Drug Discovery*
Gas Chromatography-Mass Spectrometry
Molecular Structure
Nuclear Magnetic Resonance, Biomolecular
Organisms, Genetically Modified / genetics
Organisms, Genetically Modified / metabolism*
Recombinant Proteins / metabolism
Sesquiterpenes / chemistry
Sesquiterpenes / isolation & purification
Sesquiterpenes / metabolism
Streptomyces / enzymology*
Streptomyces / genetics
Streptomyces / metabolism
Terpenes / chemistry
Terpenes / isolation & purification*
Terpenes / metabolism

Substances

Anti-Bacterial Agents
Bacterial Proteins
Diterpenes
Recombinant Proteins
Sesquiterpenes
Terpenes
Alkyl and Aryl Transferases
terpene synthase

Abstract

Publication types

MeSH terms

Substances

Grants and funding