Redirecting photosynthetic reducing power toward bioactive natural product synthesis

Agnieszka Janina Zygadlo Nielsen; Bibi Emilie Friis Ziersen; Kenneth Jensen; Lærke Marie Münter Lassen; Carl Erik Olsen; Birger Lindberg Møller; Poul Erik Jensen

doi:10.1021/sb300128r

Redirecting photosynthetic reducing power toward bioactive natural product synthesis

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

67 Citations (Scopus)

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 language	English
Journal	A C S Synthetic Biology
Volume	2
Issue number	6
Pages (from-to)	308-315
Number of pages	8
ISSN	2161-5063
DOIs	https://doi.org/10.1021/sb300128r
Publication status	Published - 21 Jun 2013

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title = "Redirecting photosynthetic reducing power toward bioactive natural product synthesis",

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.",

author = "Nielsen, {Agnieszka Janina Zygadlo} and Ziersen, {Bibi Emilie Friis} and Kenneth Jensen and Lassen, {L{\ae}rke Marie M{\"u}nter} and Olsen, {Carl Erik} and M{\o}ller, {Birger Lindberg} and Jensen, {Poul Erik}",

year = "2013",

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doi = "10.1021/sb300128r",

language = "English",

volume = "2",

pages = "308--315",

journal = "A C S Synthetic Biology",

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T1 - Redirecting photosynthetic reducing power toward bioactive natural product synthesis

AU - Nielsen, Agnieszka Janina Zygadlo

AU - Ziersen, Bibi Emilie Friis

AU - Jensen, Kenneth

AU - Lassen, Lærke Marie Münter

AU - Olsen, Carl Erik

AU - Møller, Birger Lindberg

AU - Jensen, Poul Erik

PY - 2013/6/21

Y1 - 2013/6/21

N2 - 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.

AB - 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.

U2 - 10.1021/sb300128r

DO - 10.1021/sb300128r

M3 - Journal article

SN - 2161-5063

VL - 2

SP - 308

EP - 315

JO - A C S Synthetic Biology

JF - A C S Synthetic Biology

IS - 6

ER -

Redirecting photosynthetic reducing power toward bioactive natural product synthesis

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