*Article* **Characterization, Diversity, and Structure-Activity Relationship Study of Lipoamino Acids from** *Pantoea* **sp. and Synthetic Analogues**

**Seindé Touré 1, Sandy Desrat 1, Léonie Pellissier 2, Pierre-Marie Allard 2, Jean-Luc Wolfender 2, Isabelle Dusfour 3, Didier Stien <sup>4</sup> and Véronique Eparvier 1,\***


Received: 30 January 2019; Accepted: 26 February 2019; Published: 2 March 2019

**Abstract:** A biological evaluation of a library of extracts from entomopathogen strains showed that *Pantoea* sp. extract has significant antimicrobial and insecticidal activities. Three hydroxyacyl-phenylalanine derivatives were isolated from this strain. Their structures were elucidated by a comprehensive analysis of their NMR and MS spectroscopic data. The antimicrobial and insecticidal potencies of these compounds were evaluated, and compound **3** showed 67% mortality against *Aedes aegypti* larvae at a concentration of 100 ppm, and a minimum inhibitory concentration (MIC) of 16 μg/mL against methicillin-resistant *Staphylococcus aureus*. Subsequently, hydroxyacyl-phenylalanine analogues were synthesized to better understand the structure-activity relationships within this class of compounds. Bioassays highlighted the antimicrobial potential of analogues containing saturated medium-chain fatty acids (12 or 14 carbons), whereas an unsaturated long-chain fatty acid (16 carbons) imparted larvicidal activity. Finally, using a molecular networking-based approach, several close analogues of the isolated and newly synthesized lipoamino acids were discovered in the *Pantoea* sp. extract.

**Keywords:** hydroxyacyl-phenylalanine; lipoamino acid; entomopathogen; bacteria; antimicrobial; larvicidal; *Aedes aegypti*
