Aufbau einer biosynthetischen Polyketid‐Bibliothek durch minimalinvasive Mutagenese

Abstract

Auf den Punkt mutiert: Eine Strategie der ortsgerichteten Mutagenese von Megasynthasen wurde zum Aufbau einer Polyketid‐Substanzbibliothek genutzt. Dabei wurden einfache Redoxderivatisierungen (siehe Schema) eingesetzt, um das Bioaktivitätsprofil der Verbindungen zu verändern.

Multifactorial Control of Iteration Events in a Modular Polyketide Assembly Line

“…The beauty of this rule of colinearity is that it is possible to deduce the structure of a polyketide metabolite from the organization of the PKSs and vice versa. In addition, the rule of colinearity has proven extremely valuable for rationally engineering PKSs3–6 and to predict structures of cryptic natural products from genome sequences by genome mining 7. 8 However, there are more and more deviations from this textbook knowledge; various modular PKS single domains or entire modules are skipped and individual modules may be used more than once 2.…”

Rational Design of Modular Polyketide Synthases: Morphing the Aureothin Pathway into a Luteoreticulin Assembly Line

“…[1] To warrant control over the diverse biosynthetic steps, the growing chains are covalently tethered to the template, and the functional domains are organized into a series of modules. [4] In nature, the various modular PKSs have evolved from horizontal gene transfer, gene duplications, recombinations, deletions, and mutations. The products of the condensation reaction may be processed by optional ketoreductase (KR), dehydratase (DH) and enoyl reductase (ER) domains, and eventually the final products are liberated by a thioesterase (TE) domain.…”

“…[3] This principle of colinearity has provided the ground for predicting structures from PKS genes and for rationally reprogramming the biosynthetic code for complex polyketide pathways. [4] In nature, the various modular PKSs have evolved from horizontal gene transfer, gene duplications, recombinations, deletions, and mutations. [5] Yet, such evolutionary processes await emulation in the laboratory.…”

Multifactorial Control of Iteration Events in a Modular Polyketide Assembly Line

“…[2] The beauty of this rule of colinearity is that it is possible to deduce the structure of a polyketide metabolite from the organization of the PKSs and vice versa. In addition, the rule of colinearity has proven extremely valuable for rationally engineering PKSs [3][4][5][6] and to predict structures of cryptic natural products from genome sequences by genome mining. [7,8] However, there are more and more deviations from this textbook knowledge; various modular PKS single domains or entire modules are skipped and individual modules may be used more than once.…”