Post Polyketide Synthase Carbon-Carbon Bond Formation in Type-II PKS-Derived Natural Products from Streptomyces venezuelae.
J Org Chem
; 83(4): 1876-1890, 2018 02 16.
Article
in En
| MEDLINE
| ID: mdl-29313335
ABSTRACT
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 [1-13C]-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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Streptomyces
/
Biological Products
/
Carbon
/
Polyketide Synthases
/
Fibroblasts
/
Gram-Positive Bacteria
/
Antineoplastic Agents
Limits:
Animals
/
Humans
Country/Region as subject:
America do sul
/
Venezuela
Language:
En
Journal:
J Org Chem
Year:
2018
Document type:
Article