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Combinatorial polyketide biosynthesis by de novo design and rearrangement of modular polyketide synthase genes.

Abstract：

:Type I polyketide synthase (PKS) genes consist of modules approximately 3-6 kb long, which encode the structures of 2-carbon units in polyketide products. Alteration or replacement of individual PKS modules can lead to the biosynthesis of 'unnatural' natural products but existing techniques for this are time consuming. Here we describe a generic approach to the design of synthetic PKS genes where facile cassette assembly and interchange of modules and domains are facilitated by a repeated set of flanking restriction sites. To test the feasibility of this approach, we synthesized 14 modules from eight PKS clusters and associated them in 154 bimodular combinations spanning over 1.5-million bp of novel PKS gene sequences. Nearly half the combinations successfully mediated the biosynthesis of a polyketide in Escherichia coli, and all individual modules participated in productive bimodular combinations. This work provides a truly combinatorial approach for the production of polyketides.

journal_name

Nat Biotechnol

journal_title

Nature biotechnology

authors

Menzella HG,Reid R,Carney JR,Chandran SS,Reisinger SJ,Patel KG,Hopwood DA,Santi DV

doi

10.1038/nbt1128

subject

Has Abstract

pub_date

2005-09-01 00:00:00

pages

1171-6

issue

9

eissn

1087-0156

issn

1546-1696

pii

nbt1128

journal_volume

23

pub_type

杂志文章

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