|Content of Protein Synthesis
Nonribosomal peptides are a large family of naturally
occurring compounds enzymatically synthesized from
amino acids without a nucleic acid template. Many of
these peptides have useful pharmacological properties.
Vancomycin, for example, inhibits bacterial cell wall synthesis.
Cyclosporin and precursors of penicillin are also
nonribosomal peptides. These compounds are typically
secreted by filamentous fungi, although their biological
role in the producing organism is not known.
Nonribosomal peptide synthetases (NRPSs) are large
modular proteins that assemble the amino acid units of
the metabolites. Each module is responsible for a single
catalytic step, such as activating an amino acid to its adenylate,
forming a peptide bond, or modifying a functional
group. The growing peptide is covalently attached to each
module in turn, and the N- to C-terminal order of modules
determines the organization of the final peptide product.
For example, the penicillin precursor ACV is synthesized
from modules specific for adenylate formation and attachment
of amino adipate, cysteine, and valine, in that order.
As more genes for NRPSs are identified, it should be possible
to rationally construct novel nonribosomal peptides
by genetic manipulation of modules.