title: Multivariate modular metabolic engineering for pathway and strain optimization.
abstract: Despite the potential in utilizing microbial fermentation for chemical production, the field of industrial biotechnology still lacks a standard, universally applicable principle for strain optimization. A key challenge has been in finding and applying effective ways to address metabolic flux imbalances. Strategies based on rational design require significant a priori knowledge and often fail to take a holistic view of cellular metabolism. Combinatorial approaches enable more global searches but require a high-throughput screen. Here, we present the recent advances and promises of a novel approach to metabolic pathway and strain optimization called multivariate modular metabolic engineering (MMME). In this technique, key enzymes are organized into distinct modules and simultaneously varied based on expression to balance flux through a pathway. Because of its simplicity and broad applicability, MMME has the potential to systematize and revolutionize the field of metabolic engineering and industrial biotechnology.
authors.affiliation: Manus Biosynthesis, 1030 Massachusetts Avenue, Suite 300, Cambridge, MA 02138, USA; Department of Chemical & Biological Engineering (Masters in Biotechnology Program), Northwestern University, 2145 Sheridan Road, Evanston, IL 60208, USA.
authors.forename: Bradley Walters
authors.initials: BW
authors.lastname: Biggs
authors.affiliation: Centre for Industrial Biotechnology and Biocatalysis, Ghent University, Coupure Links 653, B-9000, Belgium.
authors.forename: Brecht
authors.initials: B
authors.lastname: De Paepe
authors.affiliation: Manus Biosynthesis, 1030 Massachusetts Avenue, Suite 300, Cambridge, MA 02138, USA.
authors.forename: Christine Nicole S
authors.initials: CN
authors.lastname: Santos
authors.affiliation: Manus Biosynthesis, 1030 Massachusetts Avenue, Suite 300, Cambridge, MA 02138, USA; Centre for Industrial Biotechnology and Biocatalysis, Ghent University, Coupure Links 653, B-9000, Belgium.
authors.forename: Marjan
authors.initials: M
authors.lastname: De Mey
authors.affiliation: Manus Biosynthesis, 1030 Massachusetts Avenue, Suite 300, Cambridge, MA 02138, USA. Electronic address: pkaji@manusbio.com.
authors.forename: Parayil
authors.initials: P
authors.lastname: Kumaran Ajikumar
mesh_terms: D000475:Alkenes / Q000378:metabolism; D004224:Diterpenes / Q000378:metabolism; D005285:Fermentation; D060847:Metabolic Engineering / Q000379:methods*; D053858:Metabolic Networks and Pathways
chemical_list: D000475:Alkenes; D004224:Diterpenes; C093125:taxa-4(5),11(12)diene