Community-Directed Evolution under Orthogonal Ecological Pressures: A Conceptual Framework for Unlocking Silent Microbial Chemistry

Abstract The transcriptional silence of over 90% of biosynthetic gene clusters (BGCs) in microorganisms represents a major bottleneck for natural product discovery, as traditional screening methods have largely reached a rediscovery plateau. Here, we present a conceptual framework—Directed Experimental Evolution through Community Passaging (DEE-CP)—that redefines microbial consortia as dynamic, evolvable units amenable to guided adaptation. The central hypothesis posits that applying a Shared Biological Pressure (SBP) to hybrid microbial communities can force the system to access regions of chemical space that are inaccessible to monocultures or static co-cultures. The framework is built upon an Innovation Attribution Framework (IAF) designed to experimentally distinguish between the selection of pre-existing hidden diversity and genuine evolutionary innovation. Furthermore, we introduce the Community Coherence Index (CCI) as a diagnostic metric to monitor the emergence of inter-species metabolic communication networks. The framework adopts a staged validation approach, wherein core hypotheses are rigorously tested before advancing to higher layers of complexity, and includes a firm commitment to the publication of negative results via an open-access Null Registry. This proposal outlines a scientifically falsifiable programme designed to answer a fundamental question: what new chemistry becomes possible when evolution is guided at the level of the microbial community itself?