PRECURSOR-DIRECTED BIOSYNTHESIS OF POLYKETIDE AND NONRIBOSOMAL PEPTIDE NATURAL PRODUCTS - Modern Tools for the Synthesis of Complex Bioactive Molecules - page 484

FIGURE 14.2 Schematic overview of nonribosomal peptide biosynthesis.

As was the case in polyketide biosynthesis, several modifications are commonly
observed after the production of the peptide core. Glycosylation and acylation are
frequently seen along with cyclizations within the macrocyclic core, giving polycy-
clic compounds such as balhimycin (Section 14.4.2.1) and vancomycin [1].
While the function of NRPSs mimics that of their PKS cousins quite closely,
from an engineering standpoint, there are several key differences. Chief among these
for the approaches discussed here is the nature of the extender units. In a majority of
PKSs, the natural product is constructed from a series of condensations using simple
malonate or methylmalonate-derived extender units. In an NRPS, the extender unit
differs in each step, with the nature of this unit being dictated almost entirely by the A
domain. This organization could, in theory, allow loading unnatural analogues of a
particular amino acid onto anA domain without affecting the recruitment of extenders
by any of the other A domains.
The information presented here is by nomeans comprehensive, but provides the
basic level of understanding necessary for the comprehension of the techniques