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Dec 12, 2012 (4 years and 10 months ago)

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Bioinformatic perspectives on NRPS/PKS megasynthases: Advances
and challenges

Author(s):

Jenke
-
Kodama, H

(Jenke
-
K
odama, Holger)
1
;
Dittmann, E

(Dittmann, Elke)
1


Source:
NATURAL PRODUCT REPORTS


Volume:

26


Issue:

7


Pages:

874
-
883


DOI:

10.1039/b810283j


Published:

2009

Times Cited:

12

(from Web of Science)

Cited References:

68

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Abstract:

The increased understanding of both fundamental principles and mechanistic variations of NRPS/PKS
megasynthases along with the

unprecedented availability of microbial genome sequences has inspired a number
of in silico studies of both enzyme families. The insights that can be extracted from these analyses go far beyond
a rough classification of data and have turned bioinformatics

into a frontier field of natural products research. As
databases are flooded with NRPS/PKS gene sequences of microbial genomes and metagenomes, increasingly
reliable structural prediction methods can help to uncover hidden treasures. Already, phylogenetic

analyses have
revealed that NRPS/PKS pathways should not simply be regarded as enzyme complexes, specifically evolved to
produce a selected natural product. Rather, they represent a collection of
genetic

options, allowing biosynthetic
pathways to be shuffled in a process of perpetual chemical innovation. Understanding the principles underlying
domain specificities, protein
-
protein interactions and pathway diversification in nature can give impulses for
ge
nomic mining approaches and
genetic

engineering

of libraries of novel peptides and polyketides. The
successful translation of the knowledge obtained from bioinformatic dissection of NRPS/PKS megasynthases into
new techniques for drug discovery and design r
emain challenges for the future.

Accession Number:

WOS:000267300300002

Document Type:

Review

Language:

English

KeyWords Plus:

NONRIBOSOMAL PEPTIDE SYNTHETASE; MODULAR POLYKETIDE SYNTHASES;
PROTEIN
-
PROTEIN INTERACTIONS; BIOSYNTHESIS GENE
-
CLUSTER; ADENYLATION DOMAINS;
MICROBIAL GENOMES; SECONDARY METABOLITES; MUTATIONAL ANALYSIS; SPECIFICITY;
PREDICTION

Reprint Address:

Dittmann
, E (reprint author), Humboldt Univ, Inst Biol, Dept Mol Ecol, Chausseestr 117, D
-
10115 Berlin, Germany.

Addresses:


1. Humboldt Univ, Inst Biol, Dept Mol Ecol, D
-
10115 Berlin, Germany

E
-
mail Address:

elke.dittmann@rz.hu
-
berlin.de


Funding:

Funding Agency

Grant Number

German Research Foundation (DFG)




Evolution of Metabolic Diversity (Evomet)





[Show funding text]





Publisher:

ROYAL SOC CHEMISTRY, THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD,
CAMBRIDGE CB4 0WF, CAMBS, ENGLAND

Web of Science Categories:

Biochemistry & Molecular Biology; Chemistry, Medicinal; Chemistry, Organic

Research Areas:

Biochemistry &

Molecular Biology; Pharmacology & Pharmacy; Chemistry

IDS Number:

461VM

ISSN:

0265
-
0568