Toward a photosynthetic microbial platform for terpenoid engineering

Abstract

Plant terpenoids are among the most diverse group of naturally-occurring organic compounds known, and several are used in contemporary consumer products. Terpene synthase enzymes catalyze complex rearrangements of carbon skeleton precursors to yield thousands of unique chemical structures that range in size from the simplest five carbon isoprene unit to the long polymers of rubber. Such chemical diversity has established plant terpenoids as valuable commodity chemicals with applications in the pharmaceutical, neutraceutical, cosmetic, and food industries. More recently, terpenoids have received attention as a renewable alternative to petroleum-derived fuels and as the building blocks of synthetic biopolymers. However, the current plant- and petrochemical-based supplies of commodity terpenoids have major limitations. Photosynthetic microorganisms provide an opportunity to generate terpenoids in a renewable manner, employing a single consolidated host organism that is able to use solar energy, H2O and CO2 as the primary inputs for terpenoid biosynthesis. Advances in synthetic biology have seen important breakthroughs in microbial terpenoid engineering, traditionally via fermentative pathways in yeast and Escherichia coli. This review draws on the knowledge obtained from heterotrophic microbial engineering to propose strategies for the development of microbial photosynthetic platforms for industrial terpenoid production. The importance of utilizing the wealth of genetic information provided by nature to unravel the regulatory mechanisms of terpenoid biosynthesis is highlighted.

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Abbreviations

DMAPP:

Dimethylallyl pyrophosphate

DXP:

1-Deoxy-d-xylulose 5-phosphate

DXR:

1-Deoxy-d-xylulose 5-phosphate reductase

DXS:

1-Deoxy-d-xylulose 5-phosphate synthase

FPP:

Farnesyl pyrophosphate

GAP:

Glyceraldehyde 3-phosphate

GGPP:

Geranylgeranyl pyrophosphate

GPP:

Geranyl pyrophosphate

IDI:

Isopentenyl diphosphate isomerase

IPP:

Isopentenyl pyrophosphate

LIMS:

Limonene synthase

MEP:

Methyl-d-erythritol 4-phosphate

MVA:

Mevalonate

PTM:

Post translational modification

TPS:

Terpene synthase

SQS:

Squalene synthase

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Acknowledgments

The authors gratefully acknowledge financial support from the U.S. Department of Energy, Office of Science, Basic Energy Sciences (Grant DE-FG02-12ER16339), and the Air Force Office of Scientific Research (Grant FA9550-11-1-0211).

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Correspondence to Fiona K. Davies.

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Davies, F.K., Jinkerson, R.E. & Posewitz, M.C. Toward a photosynthetic microbial platform for terpenoid engineering. Photosynth Res 123, 265–284 (2015). https://doi.org/10.1007/s11120-014-9979-6

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Keywords

  • Terpenoid
  • Cyanobacteria
  • Metabolic engineering
  • Terpene synthase
  • MVA pathway
  • MEP pathway