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Exploiting nongenetic cell-to-cell variation for enhanced biosynthesis.

Abstract：

:Biosynthesis enables renewable production of manifold compounds, yet often biosynthetic performance must be improved for it to be economically feasible. Nongenetic, cell-to-cell variations in protein and metabolite concentrations are naturally inherent, suggesting the existence of both high- and low-performance variants in all cultures. Although having an intrinsic source of low performers might cause suboptimal ensemble biosynthesis, the existence of high performers suggests an avenue for performance enhancement. Here we develop in vivo population quality control (PopQC) to continuously select for high-performing, nongenetic variants. We apply PopQC to two biosynthetic pathways using two alternative design principles and demonstrate threefold enhanced production of both free fatty acid (FFA) and tyrosine. We confirm that PopQC improves ensemble biosynthesis by selecting for nongenetic high performers. Additionally, we use PopQC in fed-batch FFA production and achieve 21.5 g l(-1) titer and 0.5 g l(-1) h(-1) productivity. Given the ubiquity of nongenetic variation, PopQC should be applicable to a variety of metabolic pathways for enhanced biosynthesis.

journal_name

Nat Chem Biol

journal_title

Nature chemical biology

authors

Xiao Y,Bowen CH,Liu D,Zhang F

doi

10.1038/nchembio.2046

subject

Has Abstract

pub_date

2016-05-01 00:00:00

pages

339-44

issue

5

eissn

1552-4450

issn

1552-4469

pii

nchembio.2046

journal_volume

12

pub_type

杂志文章

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