Combinatorial biosynthesis--potential and problems.

Abstract:

:Because of their ecological functions, natural products have been optimized in evolution for interaction with biological systems and receptors. However, they have not necessarily been optimized for other desirable drug properties and thus can often be improved by structural modification. Using examples from the literature, this paper reviews the opportunities for increasing structural diversity among natural products by combinatorial biosynthesis, i.e., the genetic manipulation of biosynthetic pathways. It distinguishes between combinatorial biosynthesis in a narrower sense to generate libraries of modified structures, and metabolic engineering for the targeted formation of specific structural analogs. Some of the problems and limitations encountered with these approaches are also discussed. Work from the author's laboratory on ansamycin antibiotics is presented which illustrates some of the opportunities and limitations.

journal_name

J Biotechnol

journal_title

Journal of biotechnology

authors

Floss HG

doi

10.1016/j.jbiotec.2005.12.001

subject

Has Abstract

pub_date

2006-06-25 00:00:00

pages

242-57

issue

1

eissn

0168-1656

issn

1873-4863

pii

S0168-1656(05)00755-8

journal_volume

124

pub_type

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