Biomolecular Systems Engineering: Unlocking the Potential of Engineered Allostery via the Lactose Repressor Topology

Abstract

Allosteric function is a critical component of many of the parts used to construct gene networks throughout synthetic biology. In this review, we discuss an emerging field of research and education, biomolecular systems engineering, that expands on the synthetic biology edifice—integrating workflows and strategies from protein engineering, chemical engineering, electrical engineering, and computer science principles. We focus on the role of engineered allosteric communication as it relates to transcriptional gene regulators—i.e., transcription factors and corresponding unit operations. In this review, we ( a) explore allosteric communication in the lactose repressor LacI topology, ( b) demonstrate how to leverage this understanding of allostery in the LacI system to engineer non-natural BUFFER and NOT logical operations, ( c) illustrate how engineering workflows can be used to confer alternate allosteric functions in disparate systems that share the LacI topology, and ( d) demonstrate how fundamental unit operations can be directed to form combinational logical operations.