BIOTECHNOLOGICAL PRODUCTS AND PROCESS ENGINEERING Quorum sensing inhibitory activity of the metabolome from endophytic Kwoniella sp. PY016: characterization and hybrid model-based optimization Abhirup Mookherjee 1 & Ramalingam Dineshkumar 1,2 & Nithya N. Kutty 3 & Tarun Agarwal 1 & Ramkrishna Sen 1 & Adinpunya Mitra 3 & Tapas Kumar Maiti 1 & Mrinal Kumar Maiti 1 Received: 5 April 2018 /Revised: 8 June 2018 /Accepted: 10 June 2018 # Springer-Verlag GmbH Germany, part of Springer Nature 2018 Abstract Quorum sensing, the microbial communication system, is gaining importance as a therapeutic target against pathogens. The two key reasons for the rising demand of quorum sensing (QS) inhibitory molecules are low selective pressure to develop resistance by pathogens and possibility of more species-specific effects. Due to complex interactions in a unique niche of live plant tissues, endophytes, as a survival mechanism, potentially produce various bioactive compounds such as QS inhibitors. We report the isolation of an endophytic fungus Kwoniella sp. PY016 from the medicinal plant BBahera^ (Terminalia bellirica), which exhibits substantial quorum sensing inhibition and anti-biofilm activities against the standard test organism, Chromobacterium violaceum. Sugar, sugar alcohol, carboxylic acid, lipid, and phenolic classes of metabolites (predominantly xylitol) are respon- sible components of the metabolome for the desired bioactivity. A judicious combination of single-factor-at-a-time strategy and artificial neural network modeling combined with genetic algorithm was employed for the selection and optimization of the critical process and medium parameters. Through this newly adopted hybrid model-based optimization, the quorum sensing inhibitory activity of the endophytic metabolome was increased by ~ 30%. This is the first report on optimization of QS inhibitory activity from any fungal endophyte using such a hybrid advanced approach. Keywords Artificial neural network . Endophyte . Genetic algorithm . Kwoniella sp. . Metabolome . Quorum sensing inhibitor Introduction Quorum sensing is the signaling pathway-mediated re- sponse phenomenon in microorganisms to communicate with each other for certain purpose. Microbes use some small signaling molecules known as autoinducers (AI) in their quorum sensing (QS) communication (Bassler 1999). Bacterial QS is known to influence different pro- cesses, such as antibiotic production, biofilm formation, bioluminescence, competence, sporulation, and virulence factor secretion (Rutherford and Bassler 2012). Biofilm formation is one of the important phenomena of QS, which enables better survival and growth of microorgan- isms in the harsh and unfavorable environment (Costerton et al. 1999). QS inhibitors can be identified by targeting QS signal path- ways and the associated molecules (LaSarre and Federle 2013; Zhou et al. 2018). Chromobacterium violaceum wild-type (WT) strain is the most widely used biosensor for searching of QS inhibitors that affect the signaling pathway mediated by AI, such as acylhomoserine lactone (AHL) (Ghosh et al. 2014). Furthermore, a mutant Chromobacterium violaceum CV026 is also utilized for specialized screening experiments, where ex- ogenous supplementation of AHL is required for successful QS (Martin-Rodriguez et al. 2014). Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00253-018-9168-1) contains supplementary material, which is available to authorized users. * Mrinal Kumar Maiti maitimk@hijli.iitkgp.ernet.in; mrinalkmaiti@gmail.com 1 Department of Biotechnology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India 2 Department of Genetic Engineering, School of Bio-Engineering, SRM Institute of Science and Technology, Chennai, 603203, India 3 Agricultural and Food Engineering Department, Indian Institute of Technology Kharagpur, Kharagpur 721302, India Applied Microbiology and Biotechnology https://doi.org/10.1007/s00253-018-9168-1