1 research outputs found
Post Polyketide Synthase Carbon–Carbon Bond Formation in Type-II PKS-Derived Natural Products from <i>Streptomyces venezuelae</i>
Polyketide synthase (PKS) derived
natural products are biosynthesized
by head-to-tail addition of acetate and malonate extender units resulting
in linear extended-polyketide chains. Despite the well-documented
structural diversity associated with PKS-derived natural products,
C–C chain branching deviating from the usual linear pattern
is relatively rare. Herein, type-II PKS angucyclic natural products
containing a hemiaminal functionality were identified and proposed
as the parent of a series of C–C-branched analogues. These
C–C linked acetate or pyruvate branching units were located
at the α-positions on the extended polyketide chains of jadomycins
incorporating 3- and 4-aminomethylbenzoic acids. Labeling studies
utilizing [1-<sup>13</sup>C]-d-glucose provided mechanistic
evidence that the C–C bond formation occurred as a result of
a previously unidentified post-PKS processing, additional to the enzymes
encoded within the biosynthetic gene cluster. Selected compounds were
evaluated in cytotoxic or antimicrobial assays