Although natural selection led to optimal biological systems, synthetic approaches can go beyond 222 . Biological machinery provides key insights to improve biological materials production, though it also has limitations that can eventually be overcome. For instance, spider silk properties can be improved with highly hydrophobic domains, but cells are incapable of synthesizing them as their increased hydrophobicity prevents the engineered proteins from passing the endoplasmic reticulum membrane 547 . Synthetic routes can reach normal inaccessible regions of the molecular epigenetic landscapes and create new optimal materials 548-551 (Fig. ).