The search for new bioactive chemical entities is a global need due to the increasing microbial resistances to conventional antibiotics. In this context, natural products are reported as one of the most productive source for the development of new drugs. In this thesis, innovative strategies are developed to enhnance the chemodiversity of natural products and to obtain original “unnatural” natural products. First the chemical engineering of crude plant extracts is explored by means of an untargeted bromination approach. Additionally, a novel biotransformation strategy perfomed by means of the whole enzymatic machinery (secretome) obtained from the fungi B. cinerea is explored. All the reactions performed have been precisely monitored using advanced analytical techniques based on LC systems coupled to UV-ELSD-MS detectors and purified by means of geometrical gradient transfer. Among all the products generated, some biotransformed compounds have shown promising antibacterial activities.