Biosynthesis articles from across Nature Portfolio

How a lasso cyclase ties a lasso peptide into its characteristic knot has remained poorly understood. Here the authors identify key molecular interactions that guide lasso peptide folding and cyclase substrate tolerance to inform cyclase engineering for expanded lasso peptide diversity.

Integrating electrochemical CO electrolysers with a bioreactor can yield high-value long-chain carbon products, but the electrolytes for the two systems are mismatched. Now, a porous solid electrolyte reactor, which can produce acetate directly in bioelectrolyte, is demonstrated. Direct integration with a bioreactor produces bioplastic from CO via the acetate intermediate.

Modular polyketide synthases (PKSs) play a vital role in the biosynthesis of complex natural products with pharmaceutically relevant properties, and their modular architecture makes them an attractive target for engineering to produce platform chemicals and drugs. In this study, the authors demonstrate that the promiscuous malonyl/acetyl-transferase domain (MAT) from murine fatty acid synthase serves as a highly versatile tool for the production of polyketide analogs.

Assembly-line polyketide synthases perform modular enzymatic synthesis of medically important natural products. In this study, the authors used site-selective crosslinking to probe structural states that reveal how substrate carrier proteins interact with successive modules in a representative assembly line.

Although biosynthetic pathways of selenium-containing macromolecules have been known for decades, pathways for specific incorporation of selenium into small molecules have only recently begun to be uncovered. Now the selenometabolome is expanded further through the discovery and biosynthetic elucidation of ovoselenol, a selenium-containing antioxidant found in marine microorganisms.

The biosynthetic intermediate of the common core of enediyne natural products has been enigmatic for decades. Now, researchers report the identification of a diiodotetrayne compound as the universal enediyne biosynthetic intermediate.

The iterative operation of certain polyketide synthase modules is demonstrated in vitro using a combination of protein biochemistry, synthesis of biosynthetic intermediates, and mass spectrometric analysis.

Peptides are fundamental in life and are widely used as therapeutic agents; however, they are problematic to produce by chemical synthesis. The discovery of unusual biosynthetic pathways that produce peptide natural products reveals an alternative approach for peptide synthesis that uses ‘standalone’ ligase enzymes rather than multimodular enzymes.

John Steele and Stephen Wallace discuss recent advances in the chemical and biotechnological synthesis of the prolific platform chemical adipic acid.