Biology subjects

Khoshouei, A.

Publications and source records attributed to Khoshouei, A..

3 recordsLinked to original sources

bioRxiv2026

Acyl amides derived from a bacterial symbiont control development of its nematode host

Symbiotic bacteria frequently regulate host development through small-molecule signals. In the entomopathogenic Steinernema nematode - Xenorhabdus bacterium symbiosis, which is widely used in biological pest control, the signals that trigger nematode development have remained unknown. Using a phenotypic screen of Xenorhabdus mutants, we identified bacterial acyl amides, which we named stripteamides, as signals required for efficient recovery of Steinernema infective juveniles. Stripteamides are synthesized from phenylethylamine and activated fatty acid substrates by StaS, a previously uncharacterized amide synthase. Mechanistic and structural analyses indicate that StaS evolved from the initiation module of a nonribosomal peptide synthetase (NRPS) and was repurposed to generate signaling metabolites for host development. Stripteamide signaling is conserved across Xenorhabdus species and operates in different Steinernema hosts. These findings reveal a new function for widespread bacterial acyl amides that previously have been shown as cytotoxic and affecting bacterial quorum sensing, highlighting the context dependence of microbial natural product language.

microbiology↗

bioRxiv2026

Disentangling the sucrose metabolism of the corn smut Ustilago maydis reveals unexpected complexity

The race for carbohydrates shapes organismic interactions. In plant pathogenic fungi, sucrose is a key nutrient as it constitutes the major transport sugar in plants. Here, we investigate sucrose acquisition in the corn smut fungus Ustilago maydis, a biotrophic pathogen that transitions from yeast-like to hyphal growth for infection. We establish that the fungus encodes a secreted acidic invertase, Suc2, with a dimeric canonical glycoside hydrolase 32 architecture. Comparative biochemical analyses across fungal homologs indicate that this dimeric architecture represents the predominant state, whereas higher-order oligomers, as initially described for Saccharomyces cerevisiae Suc2, are restricted to a subset of lineages. Unexpectedly, elimination of Suc2 did not impair yeast-like growth on sucrose. Similarly, deletion of genes for sucrose transporter Srt1 and cytosolic hydrolase Suc1, typically associated with intracellular sucrose metabolism, did not abolish growth. Instead, sucrose utilization during yeast-like growth depended on a repurposed non-canonical module comprising maltose transporter Agt1 and intracellular (iso)maltases. In contrast, pathogenic development strongly relied on the canonical intracellular sucrose utilization pathway mediated by Srt1 and Agt1. Infection was strongly diminished in strains unable to metabolise sucrose, confirming its central nutritional role for the fungus. Together, our work defines the complete sucrose utilization repertoire of U. maydis and uncovers a lifestyle-dependent metabolic switch between alternative sucrose acquisition strategies. Flexible carbon acquisition might represent a widespread adaptive strategy in basidiomycete pathogenic fungi.

microbiology↗

bioRxiv2023

Efficient and scalable de novo protein design using a relaxed sequence space

Deep learning techniques are being used to design new proteins by creating target backbone geometries and finding sequences that can fold into those shapes. While methods like ProteinMPNN provide an efficient algorithm for generating sequences for a given protein backbone, there is still room for improving the scope and computational efficiency of backbone generation. Here, we report a backbone hallucination protocol that uses a relaxed sequence representation. Our method enables protein backbone generation using a gradient descent driven hallucination approach and offers orders-of-magnitude efficiency enhancements over previous hallucination approaches. We designed and experimentally produced over 50 proteins, most of which expressed well in E. Coli, were soluble and adopted the desired oligomeric state along with the correct composition of secondary structure as measured by CD. Exemplarily, we determined 3D electron density maps using single-particle cryo EM analysis for three single-chain de-novo proteins comprising 600 AA which closely matched with the designed shape. These have no structural analogues in the protein data bank (PDB), representing potentially novel folds or arrangement of domains. Our approach broadens the scope of de novo protein design and contributes to accessibility to a wider community.

synthetic biology↗