TY - JOUR

T1 - Multiplex Genome Engineering for Optimizing Bioproduction in Saccharomyces cerevisiae

AU - Auxillos, Jamie Y.

AU - Garcia-Ruiz, Eva

AU - Jones, Sally

AU - Li, Tianyi

AU - Jiang, Shuangying

AU - Dai, Junbiao

AU - Cai, Yizhi

N1 - Funding Information: *E-mail: yizhi.cai@manchester.ac.uk. ORCID Junbiao Dai: 0000-0002-5299-4700 Yizhi Cai: 0000-0003-1663-2865 Funding The work is funded through a Biotechnology and Biological Sciences Research Council grant (BB/P02114X/1), a Bill & Melinda Gates Foundation award (RB0447), and the University of Manchester President’s Award for Research Excellence to Y.C. J.Y.A. is jointly supported by a graduate fellowship from the Bill & Melinda Gates Foundation and the University of Manchester. This work was also supported by the National Science Fund for Distinguished Young Scholars (31725002), by the Bureau of International Cooperation, Chinese Academy of Sciences (172644KYSB20170042), and by the Key Research Program of the Chinese Academy of Science (KFZD-SW-215) (to J.D.). Notes The authors declare no competing financial interest. Publisher Copyright: © 2019 American Chemical Society.

PY - 2019/3/19

Y1 - 2019/3/19

N2 - The field of synthetic biology is already beginning to realize its potential, with a wealth of examples showcasing the successful genetic engineering of microorganisms for the production of valuable compounds. The chassis Saccharomyces cerevisiae has been engineered to function as a microfactory for producing many of these economically and medically relevant compounds. However, strain construction and optimization to produce industrially relevant titers necessitate a wealth of underpinning biological knowledge alongside large investments of capital and time. Over the past decade, advances in DNA synthesis and editing tools have enabled multiplex genome engineering of yeast, permitting access to more complex modifications that could not have been easily generated in the past. These genome engineering efforts often result in large populations of strains with genetic diversity that can pose a significant challenge to screen individually via traditional methods such as mass spectrometry. The large number of samples generated would necessitate screening methods capable of analyzing all of the strains generated to maximize the explored genetic space. In this Perspective, we focus on recent innovations in multiplex genome engineering of S. cerevisiae, together with biosensors and high-throughput screening tools, such as droplet microfluidics, and their applications in accelerating chassis optimization.

AB - The field of synthetic biology is already beginning to realize its potential, with a wealth of examples showcasing the successful genetic engineering of microorganisms for the production of valuable compounds. The chassis Saccharomyces cerevisiae has been engineered to function as a microfactory for producing many of these economically and medically relevant compounds. However, strain construction and optimization to produce industrially relevant titers necessitate a wealth of underpinning biological knowledge alongside large investments of capital and time. Over the past decade, advances in DNA synthesis and editing tools have enabled multiplex genome engineering of yeast, permitting access to more complex modifications that could not have been easily generated in the past. These genome engineering efforts often result in large populations of strains with genetic diversity that can pose a significant challenge to screen individually via traditional methods such as mass spectrometry. The large number of samples generated would necessitate screening methods capable of analyzing all of the strains generated to maximize the explored genetic space. In this Perspective, we focus on recent innovations in multiplex genome engineering of S. cerevisiae, together with biosensors and high-throughput screening tools, such as droplet microfluidics, and their applications in accelerating chassis optimization.

UR - http://www.scopus.com/inward/record.url?scp=85062833483&partnerID=8YFLogxK

U2 - 10.1021/acs.biochem.8b01086

DO - 10.1021/acs.biochem.8b01086

M3 - Review

C2 - 30817136

AN - SCOPUS:85062833483

VL - 58

SP - 1492

EP - 1500

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 11

ER -