Nothing in biology makes sense except in the light of evolution‰ is a famous statement of the evolutionary biologist Theodosius Dobzhansky almost four decades ago. Unquestionably, this statement has had a profound impact on generations of biologists and biochemists and continues to do so. However, the relevance of evolution as the theoretical foundation of biology to the applied aspects of the biological sciences (for instance, in the development of bioinformatic s pipelines and biotechnological applications) has largely been neglected. In this seminar, I will argue that evolutionary principles can be exploited to generate novel bioinformatic approaches that can guide the discovery of novel natural products, as well as highly constrained novel antibiotic targets that are less prone to evolve antibiotic resistance. These approaches find their metabolic foundations on GSMR, which in turn can be exploited to understand bacterial speciation. Moreover, since the occurrence of enzyme promiscuity, and its relationship with protein conformational diversity, plays a central role in the approaches I will be discussing, this biological phenomenon will also be discussed in both theoretical and experimental grounds. In particular, an unpublished episode of enzyme sub-functionalization through conformational diversity after differential gene gain-and-loss in bacteria will be presented.