DNA assembly techniques for next-generation combinatorial biosynthesis of natural products.

Abstract:

:Natural product scaffolds remain important leads for pharmaceutical development. However, transforming a natural product into a drug entity often requires derivatization to enhance the compound's therapeutic properties. A powerful method by which to perform this derivatization is combinatorial biosynthesis, the manipulation of the genes in the corresponding pathway to divert synthesis towards novel derivatives. While these manipulations have traditionally been carried out via restriction digestion/ligation-based cloning, the shortcomings of such techniques limit their throughput and thus the scope of corresponding combinatorial biosynthesis experiments. In the burgeoning field of synthetic biology, the demand for facile DNA assembly techniques has promoted the development of a host of novel DNA assembly strategies. Here we describe the advantages of these recently developed tools for rapid, efficient synthesis of large DNA constructs. We also discuss their potential to facilitate the simultaneous assembly of complete libraries of natural product biosynthetic pathways, ushering in the next generation of combinatorial biosynthesis.

authors

Cobb RE,Ning JC,Zhao H

doi

10.1007/s10295-013-1358-3

subject

Has Abstract

pub_date

2014-02-01 00:00:00

pages

469-77

issue

2

eissn

1367-5435

issn

1476-5535

journal_volume

41

pub_type

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