Reactivity and mechanism in chemical and synthetic biology

Physical organic chemistry and mechanistic thinking provide a strong intellectual framework for understanding the chemical logic of evolvable informational macromolecules and metabolic transformations in living organisms. These concepts have also led to numerous successes in designing and applying tools to delineate biological function in health and disease, chemical ecology and possible alternative chemistries employed by extraterrestrial life. A symposium at the 2020 Pacifichem meeting was scheduled in December 2020 to discuss designing and exploiting expanded genetic alphabets, methods to understand the biosynthesis of natural products and re-engineering primary metabolism in bacteria. The COVID-19 pandemic led to postponement of in-person discussions, with the symposium eventually being held on 20-21 December 2021 as an online event. This issue is a written record of work presented on biosynthetic pathways and enzyme catalysis, engineering microorganisms with new metabolic capabilities, and the synthesis of non-canonical, nucleobases for medical applications and for studies of alternate chemistries for living organisms. The variety of opinion pieces, reviews and original research articles provide a starting point for innovations that clarify how complex biological systems emerge from the rules of chemical reactivity and mechanism.This article is part of the themed issue 'Reactivity and mechanism in chemical and synthetic biology'.

Automated summary

Physical organic chemistry and mechanistic thinking are instrumental in understanding the chemical processes and metabolic transformations in living organisms. They have also contributed to advancements in the fields of biological function, chemical ecology, and alternative chemistries. The symposium initially planned for December 2020 was postponed due to the COVID-19 pandemic and held as an online event in December 2021. This themed issue showcases research on biosynthetic pathways, enzyme catalysis, genetic alphabets, and alternative chemistries, providing a foundation for understanding the emergence of complex biological systems.