Metabolic engineering in isoquinoline alkaloid biosynthesis.

Abstract:

:Higher plants produce diverse classes of metabolites. Metabolic engineering offers tremendous potential to improve the production and quality of these chemicals. This report summarizes the possibility of using metabolic engineering in benzylisoquinoline alkaloid biosynthesis. Benzylisoquinoline alkaloids, such as morphine, sanguinarine, and berberine, are synthesized from tyrosine via reticuline in Magnoliaceae, Ranunculaceae, Berberidaceae, Papaveraceae, and many other species. The early pathway from tyrosine to reticuline is common among many plant species, whereas there is more diversity in late pathways. This review describes several strategies to improve the yield and quality of benzylisoquinoline alkaloids. First, the overexpression of a rate-limiting enzyme in an early pathway to increase the overall alkaloid yield is discussed. Second, the introduction of a new branch into the pathway has been shown to produce novel metabolites. Finally, the possibility of accumulating a pathway intermediate by the knock-down of a key step is examined. Further metabolic modification is also discussed, since the latter two modifications may lead to the production of novel compound(s) from an accumulated intermediate through metabolic activation. These metabolic changes could be further modified to increase chemical diversity through somatic variation in cell culture. Besides this direct metabolic engineering with isolated biosynthetic genes, the regulation of biosynthetic activity with transcription factors and/or with reconstruction of the entire biosynthesis will also be discussed for the next generation of metabolite production.

journal_name

Curr Pharm Biotechnol

authors

Sato F,Inui T,Takemura T

doi

10.2174/138920107781387438

subject

Has Abstract

pub_date

2007-08-01 00:00:00

pages

211-8

issue

4

eissn

1389-2010

issn

1873-4316

journal_volume

8

pub_type

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