# Impact of the Deletion of Genes of the Nitrogen Metabolism on Triacylglycerol, Cardiolipin and Actinorhodin Biosynthesis in Streptomyces coelicolor

## TL;DR

Deleting certain nitrogen metabolism genes in Streptomyces coelicolor affects lipid and pigment production, possibly reducing oxidative stress.

## Contribution

The study reveals novel connections between nitrogen metabolism gene deletions and altered biosynthesis of TAG, CL, and ACT in Streptomyces coelicolor.

## Key findings

- Deleting genes involved in nitrogen metabolism increased triacylglycerol (TAG) content in some Streptomyces coelicolor strains.
- Cardiolipin (CL) content decreased in several gene-deleted strains compared to the original strain.
- Actinorhodin (ACT) production was abolished in the dasR mutant and increased in others, depending on Pi conditions.

## Abstract

Since nitrogen limitation is known to be an important trigger of triacylglycerol (TAG) accumulation in most microorganisms, we first assessed the global lipid content of 21 strains derived from Streptomyces coelicolor M145 deleted for genes involved in nitrogen metabolism. Seven of these strains deleted for genes encoding proteins involved in polyamine (GlnA2/SCO2241, GlnA3/SCO6962, GlnA4/SCO1613), or protein (Pup/SCO1646) degradation, in the regulation of nitrogen metabolism (GlnE/SCO2234 and GlnK/SCO5584), or the global regulator DasR/SCO5231 that controls negatively the degradation of N-acetylglucosamine, a constituent of peptidoglycan, had a higher TAG content than the original strain, whereas five of these strains (except the glnA2 and pup mutants) had a lower cardiolipin (CL) content. The production of the blue polyketide actinorhodin (ACT) was totally abolished in the dasR mutant in both Pi conditions, whereas the deletion of pup, glnA2, glnA3, and glnA4 was correlated with a significant increase in total ACT production, but mainly in Pi limitation. Unexpectedly, ACT production was strongly reduced in the glnA3 mutant in Pi proficiency. Altogether, our data suggest that high TAG and ACT biosynthesis and low CL biosynthesis might all contribute to the lowering of oxidative stress resulting from nitrogen limitation or from other causes.