The unique mechanistic transformations involved in the biosynthesis of modular natural products from marine cyanobacteria

Abstract

Cyanobacteria are abundant producers of natural products well recognized for their bioactivity and utility in drug discovery and biotechnology applications. In the last decade, characterization of several modular gene clusters that code for the biosynthesis of these compounds has revealed a number of unusual enzymatic reactions. In this article, we review several mechanistic transformations identified in marine cyanobacterial biosynthetic pathways, with an emphasis on modular polyketide synthase(PKS)/non-ribosomal peptide synthetase (NRPS) gene clusters. In selected instances, we also make comparisons between cyanobacterial gene clusters derived from marine and freshwater strains. We then provide an overview of recent developments in cyanobacterial natural products biosynthesis made available through genome sequencing and new advances in bioinformatics and genetics.

Genomic insights into the physiology and ecology of the marine filamentous cyanobacterium Lyngbya majuscula

“…We also explored the ability of L. majuscula 3L to assimilate atmospheric nitrogen through 15 N isotope feeding experiments. L. majuscula 3L filaments were grown in media containing 15 Nlabeled sodium nitrate for ∼21 d until nitrogen-containing compounds were fully labeled with this heavy isotope, as assessed by MALDI/TOF mass spectrometry of the metabolome (Materials and Methods).…”

“…The fully 15 N-labeled filaments were then grown in nitrate-free media for 10 d, and the incorporation of the prevailing natural 14 N isotope from atmospheric N 2 into nitrogen-containing compounds was evaluated using MALDI/MS. The shift from 15 N to 14 N was calculated for pheophytin a, a chlorophyll breakdown product that readily ionizes during MALDI analysis of Lyngbya filaments (Fig. 3C, ref.…”

“…L. majuscula 3L filaments were grown in media containing 15 Nlabeled sodium nitrate for ∼21 d until nitrogen-containing compounds were fully labeled with this heavy isotope, as assessed by MALDI/TOF mass spectrometry of the metabolome (Materials and Methods). The fully 15 N-labeled filaments were then grown in nitrate-free media for 10 d, and the incorporation of the prevailing natural 14 N isotope from atmospheric N 2 into nitrogen-containing compounds was evaluated using MALDI/MS.…”

“…In the last 10 y, focused investigations into the biosynthesis of L. majuscula natural products have revealed gene clusters that encode the molecular assembly of several of these compounds, including the anticancer agent curacin A (9-11), the neurotoxic jamaicamides (12), the UV-sunscreen pigment scytonemin (13), and the lyngbyatoxins (14), dermatotoxic agents responsible for "swimmer's itch." Most of the gene clusters encode modular, mixed polyketide synthase (PKS)/nonribosomal peptide synthetase (NRPS) assembly lines, with several using highly unusual mechanisms to incorporate other functional groups into the resultant molecules (15).…”

Cianobactérias: uma revisão sobre potencial nutricional e alguns aspectos biotecnológicos

“…Isso tem permitido o crescimento da aplicação biotecnológica desses metabolitos, uma vez que, tem aumentado o conhecimento de como estas moléculas são feitas, bioquímica e geneticamente (JONES et al, 2009;JONES et al, 2010).…”