Abstract
The pharmaceutically important anticancer drugs etoposide and teniposide are derived from
podophyllotoxin, a natural product isolated from roots of Podophyllum hexandrum growing
in the wild. The overexploitation of this endangered plant has led to the search for alternative
sources. Metabolic engineering aimed at constructing the pathway in another host cell
is very appealing, but for that approach, an in-depth knowledge of the pathway toward
podophyllotoxin is necessary. In this chapter, we give an overview of the lignan pathway
leading to podophyllotoxin. Subsequently, we will discuss the engineering possibilities to
produce podophyllotoxin in a heterologous host. This will require detailed knowledge on
the cellular localization of the enzymes of the lignan biosynthesis pathway. Due to the high
number of enzymes involved and the scarce information on compartmentalization, the
heterologous production of podophyllotoxin still remains a tremendous challenge. At the
moment, research is focusing on the last step(s) in the conversion of deoxypodophyllotoxin
to (epi)podophyllotoxin and 4′-demethyldesoxypodophyllotoxin by plant cytochromes.
Keywords: etoposide, podophyllotoxin, Podophyllum hexandrum, Anthriscus sylvestris,
metabolic engineering
podophyllotoxin, a natural product isolated from roots of Podophyllum hexandrum growing
in the wild. The overexploitation of this endangered plant has led to the search for alternative
sources. Metabolic engineering aimed at constructing the pathway in another host cell
is very appealing, but for that approach, an in-depth knowledge of the pathway toward
podophyllotoxin is necessary. In this chapter, we give an overview of the lignan pathway
leading to podophyllotoxin. Subsequently, we will discuss the engineering possibilities to
produce podophyllotoxin in a heterologous host. This will require detailed knowledge on
the cellular localization of the enzymes of the lignan biosynthesis pathway. Due to the high
number of enzymes involved and the scarce information on compartmentalization, the
heterologous production of podophyllotoxin still remains a tremendous challenge. At the
moment, research is focusing on the last step(s) in the conversion of deoxypodophyllotoxin
to (epi)podophyllotoxin and 4′-demethyldesoxypodophyllotoxin by plant cytochromes.
Keywords: etoposide, podophyllotoxin, Podophyllum hexandrum, Anthriscus sylvestris,
metabolic engineering
| Original language | English |
|---|---|
| Title of host publication | Medicine : Natural Products and Cancer Drug Discovery |
| Publisher | InTech |
| ISBN (Electronic) | 978-953-51-3314-8 |
| ISBN (Print) | 978-953-51-3313-1, |
| DOIs | |
| Publication status | Published - 2017 |