Non-ribosomal peptides are a diverse and medically important group of natural products. They are biosynthesised by modular non-ribosomal peptide synthetase (NRPS) assembly-lines in which domains from each module act in concert to incorporate a specific amino acid into a peptide. This modular biosynthesis has driven efforts to generate new peptide analogues by substituting amino acid specifying domains. Rational NRPS engineering has increasingly focused on using evolutionarily favoured recombination sites for domain substitution. As has been shown by directed evolution, sometimes the most rational approach is to accept the inherent noisiness and to use semi-rational approaches that focuses on volume. Here, I present our labs work on an alternative evolution-inspired approach, focused on large scale diversification and screening. By amplifying amino acid specifying domains from soil-derived metagenomic DNA, we leveraged natural diversity for the parallel substitution of over 1,000 unique domains into a pyoverdine NRPS. Screening via fluorescence and mass spectrometry followed by sequencing identified more than 100 functional domain substitutions that collectively yielded 16 unique pyoverdines as major products. This metagenomic approach shifts the problem of engineering non-ribosomal peptide biosynthesis from necessitating a high success rate of individual domain substitution to developing effective high-throughput screens.