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Combinatorial Biosynthesis of Polyketides--a Perspective

Overview
Publisher Elsevier
Specialty Biochemistry
Date 2012 Feb 21
PMID 22342766
Citations 48
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Abstract

Since their discovery, polyketide synthases have been attractive targets of biosynthetic engineering to make 'unnatural' natural products. Although combinatorial biosynthesis has made encouraging advances over the past two decades, the field remains in its infancy. In this enzyme-centric perspective, we discuss the scientific and technological challenges that could accelerate the adoption of combinatorial biosynthesis as a method of choice for the preparation of encoded libraries of bioactive small molecules. Borrowing a page from the protein structure prediction community, we propose a periodic challenge program to vet the most promising methods in the field, and to foster the collective development of useful tools and algorithms.

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References
1.
Zucko J, Cullum J, Hranueli D, Long P . Evolutionary dynamics of modular polyketide synthases, with implications for protein design and engineering. J Antibiot (Tokyo). 2010; 64(1):89-92. DOI: 10.1038/ja.2010.141. View

2.
Starcevic A, Diminic J, Zucko J, Elbekali M, Schlosser T, Lisfi M . A novel docking domain interface model predicting recombination between homoeologous modular biosynthetic gene clusters. J Ind Microbiol Biotechnol. 2010; 38(9):1295-304. DOI: 10.1007/s10295-010-0909-0. View

3.
Starcevic A, Zucko J, Simunkovic J, Long P, Cullum J, Hranueli D . ClustScan: an integrated program package for the semi-automatic annotation of modular biosynthetic gene clusters and in silico prediction of novel chemical structures. Nucleic Acids Res. 2008; 36(21):6882-92. PMC: 2588505. DOI: 10.1093/nar/gkn685. View

4.
Staunton J, Weissman K . Polyketide biosynthesis: a millennium review. Nat Prod Rep. 2001; 18(4):380-416. DOI: 10.1039/a909079g. View

5.
Ellis T, Adie T, Baldwin G . DNA assembly for synthetic biology: from parts to pathways and beyond. Integr Biol (Camb). 2011; 3(2):109-18. DOI: 10.1039/c0ib00070a. View