A 'Genome-First' Framework for Next-Generation Bioinputs: From Functional Mining to Rational Synthetic Microbial...

The demand for sustainable agriculture has shifted bioprospecting towards microbial bioinputs as alternatives to chemical fertilisers and pesticides. Whole-genome sequencing accelerates the discovery of plant-growth-promoting bacteria (PGPB) by enabling the identification of functional genes and the prediction of traits such as nutrient solubilisation, phytohormone production and biocontrol. Traditionally a secondary tool for strain characterisation, genomics has evolved into a 'genome-first' strategy that effectively collapses the phenotypic bottleneck in prospective bioprospecting and the rational design of synthetic microbial communities (SynComs). In this review, we argue for a transition from empirical phenotypic screening towards a genomics-guided paradigm for the selection of next-generation bioinputs. This work demonstrates how actionable insights can be gained through the integration of high-resolution genome mining into discovery pipelines. We explore the application of reverse ecology to infer ecological roles from genomic content and emphasise the critical role of pangenomics in identifying traits linked to host colonisation and niche adaptation. Furthermore, we advocate for biosafety screening as a non-negotiable prerequisite for bioinoculant development to ensure ecological and clinical safety. Finally, this work proposes that genome-scale metabolic networks are essential to enable the transition from single-strain inoculants to the assembly of stable SynComs. This framework establishes a comprehensive, data-driven approach to predictable interventions in the agricultural bioeconomy.