Intersecting xenobiology and neo-metabolism to bring novel chemistries to life

The life diversity relies on a handful chemical elements (carbon, oxygen, hydrogen, nitrogen, sulphur and phosphorus) as part of essential building blocks, whereas other atoms are needed to a lesser extent and most of the remaining elements are excluded from biology. This circumstance limits the scope of biochemical reactions in extant metabolism - yet it offers a phenomenal playground for synthetic biology. Xenobiology aims at bringing novel bricks to life that could be exploited towards (xeno)metabolite synthesis. In particular, the assembly of novel pathways engineered to handle non-biological elements (neo-metabolism) will broaden the chemical space beyond the reach of natural evolution. In this review, xeno-elements that could be blended into Nature's biosynthetic portfolio are discussed together with their physicochemical properties and tools and strategies to incorporate them into biochemistry. We argue that current bioproduction methods can be revolutionized by intersecting xenobiology with neo-metabolism for the synthesis of new-to-Nature molecules, e.g. organohalides.