| | |  | | | | Record from Web of Science® | | | | | | |
| Combinatorial polyketide biosynthesis by de novo design and rearrangement of modular polyketide synthase genes |
|
|
| Author(s): Menzella HG, Reid R, Carney JR, Chandran SS, Reisinger SJ, Patel KG, Hopwood DA, Santi DV |
| Source: NATURE BIOTECHNOLOGY Volume: 23 Issue: 9 Pages: 1171-1176 Published: SEP 2005 |
| Times Cited: 66 References: 30 |
| Abstract: Type I polyketide synthase (PKS) genes consist of modules similar to 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. |
| Document Type: Article |
| Language: English |
| Reprint Address: Santi, DV (reprint author), Kosan Biosci Ins, 3832 Bay Ctr Pl, Hayward, CA 94545 USA |
Addresses:
1. Kosan Biosci Ins, Hayward, CA 94545 USA
2. John Innes Ctr, Dept Mol Microbiol, Norwich NR4 7UH, Norfolk England |
| Publisher: NATURE PUBLISHING GROUP, 345 PARK AVENUE SOUTH, NEW YORK, NY 10010-1707 USA |
| Subject Category: Biotechnology & Applied Microbiology |
| IDS Number: 963GA |
| ISSN: 1087-0156 |
| DOI: 10.1038/nbt1128 |
|
| | | | | | | | | Record from Web of Science® | | | | | | | | | |