Divergolides A–D from a Mangrove Endophyte Reveal an Unparalleled Plasticity in ansa‐Macrolide Biosynthesis

Abstract

Eingebaute Diversität: Aus dem bakteriellen Endophyten des Mangroven‐Baums Bruguiera gymnorrhiza wurden vier Ansamakrolide mit ungewöhnlichen Strukturen isoliert. Die Analyse der Kohlenstoffgerüste dieser Divergolide A–D (1–4) deutet auf eine gemeinsame Biogenese hin, ausgehend von einer linearen Vorstufe, die verschiedene polycyclische Strukturen aufbauen kann. Diese beachtliche Flexibilität in der Biosynthese führt zu Metaboliten, die sich in ihren Bioaktivitätsprofilen unterscheiden und antibakterielle und zytotoxische Eigenschaften abdecken.

A Branched Extender Unit Shared between Two Orthogonal Polyketide Pathways in an Endophyte

“…In the course of evaluating the metabolic capabilities of mangrove endophytes, [19] we have discovered a set of unusual ansa macrolides, named divergolides, which differ markedly in their overall architecture but share an unprecedented branched side chain. [20] This unusual residue suggested that the polyketide backbone has incorporated a novel type of branched extender unit that is likely derived from isobutyrate. Initial attempts to support this hypothesis through stableisotope labeling failed because of the minute amounts of divergolides produced.…”

A Branched Extender Unit Shared between Two Orthogonal Polyketide Pathways in an Endophyte

“…[20] This unusual residue suggested that the polyketide backbone has incorporated a novel type of branched extender unit that is likely derived from isobutyrate. Initial attempts to support this hypothesis through stableisotope labeling failed because of the minute amounts of divergolides produced.…”

Regiodivergent NC and NN Aryl Coupling Reactions of Indoloterpenes and Cycloether Formation Mediated by a Single Bacterial Flavoenzyme

“…Only recently, in the context of profiling the bacterial endophytes of widespread mangrove trees, [1] we discovered the unprecedented bacterial indolosesquiterpenes xiamycin (1), indosespene (2), and sespenine (3; Figure 1). Interestingly, these alkaloids are a hallmark of plant and fungal metabolism, but virtually nothing was known about the corresponding bacterial pathways.…”