Redirecting Photosynthetic Reducing Power toward Bioactive Natural Product Synthesis

Agnieszka Zygadlo Nielsen, Bibi Ziersen, Kenneth Jensen, Lærke Münter Lassen, Carl Erik Olsen, Birger Lindberg Møller, Poul Erik Jensen

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

In addition to the products of photosynthesis, the chloroplast provides the energy and carbon building blocks required for synthesis of a wealth of bioactive natural products of which many have potential uses as pharmaceuticals. In the course of plant evolution, energy generation and biosynthetic capacities have been compartmentalized. Chloroplast photosynthesis provides ATP and NADPH as well as carbon sources for primary metabolism. Cytochrome P450 monooxygenases (P450s) in the endoplasmic reticulum (ER) synthesize a wide spectrum of bioactive natural products, powered by single electron transfers from NADPH. P450s are present in low amounts, and the reactions proceed relatively slowly due to limiting concentrations of NADPH. Here we demonstrate that it is possible to break the evolutionary compartmentalization of energy generation and P450-catalyzed biosynthesis, by relocating an entire P450-dependent pathway to the chloroplast and driving the pathway by direct use of the reducing power generated by photosystem I in a light-dependent manner. The study demonstrates the potential of transferring pathways for structurally
complex high-value natural products to the chloroplast and directly tapping into the reducing power generated by photosynthesis to drive the P450s using water as the primary electron donor.
Original languageEnglish
JournalA C S Synthetic Biology
Volume2
Issue number6
Pages (from-to)308-315
ISSN2161-5063
DOIs
Publication statusPublished - 2013
Externally publishedYes

Keywords

  • Light-driven biosynthesis
  • Plant biology
  • Metabolic engineering
  • Natural products production
  • Photosynthesis
  • Chloroplast

Fingerprint Dive into the research topics of 'Redirecting Photosynthetic Reducing Power toward Bioactive Natural Product Synthesis'. Together they form a unique fingerprint.

Cite this