Nonribosomal code: Difference between revisions

Revision as of 17:24, 12 May 2014

Revision as of 17:28, 12 May 2014

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The '''nonribosomal code''' refers to key amino acid residues and their positions within the primary sequence of an adenylation ___domain of a [[nonribosomal peptide synthetase]] in orderused to predict substrate specificity and thus (partially) the final product. Analogous to the nonribosomal code is prediction of peptide composition by DNA/RNA codon reading, which is well supported by the [[central dogma of molecular biology]] and accomplished using the genetic code simply by following the [[DNA codon table]] or [[RNA codon table]]. However, prediction of natural product/secondary metabolites by the nonribosomal code is not as concrete as DNA/RNA codon-to-amino acid and much research is still needed to have a broad-use code. The increasing number of sequenced genomes and high-throughput prediction software has allowed for better elucidation of predicted substrate specificity and thus natural products/secondary metabolites. Enzyme characterization by, for example, ATP-pyrophosphate exchange assays for substrate specificity and ''in silico'' substrate-binding pocket modelling helps support predictive algorithms. Much research has been done on bacteria and fungi, with prokaryotic bacteria having easier-to-predict products.

The nonribosomal peptide synthetase (NRPS), a multi-modular enzyme complex classically contains repeating, tri-domains (adenylation (A), peptidyl carrier protein (PCP) and lastly codensation(C)). The adenylation ___domain (A) is the focus for substrate specificity since it is the initiating and substrate recognition ___domain. The NRPS collinearity principle/rule dictates that given the order of adenylation domains (and substrate-specificity code) throughout the NRPS one can predict the amino acid sequence of the produced small peptide. NRPS, NRPS-like or NRPS-PKS complexes also exist and have ___domain variations, additions and/or exclusions.