Metabolic engineering

Metabolic engineering is the deliberate alteration of the networks of chemical reactions inside cells, usually microbes, so that they produce a desired compound efficiently. Using recombinant DNA and genome editing, engineers add genes for enzymes from other organisms, raise the expression of bottleneck enzymes, delete genes that divert material into unwanted by-products and adjust regulation and transport. The field took shape in the early 1990s, building on older strain improvement by random mutation and selection.

The work runs in repeated design, build, test and learn cycles. Models of metabolic flux, the flow of material through a pathway, help predict which changes will help, and promoters and ribosome binding sites are tuned to balance enzyme levels, since too much of one enzyme can waste resources or let toxic intermediates build up. Success is judged by titer, rate and yield: how much product accumulates, how fast, and how much is made per unit of feedstock. The best strains are then grown in bioreactors.

A celebrated example is the antimalarial drug artemisinin, normally extracted from sweet wormwood. Researchers moved plant genes into baker's yeast and boosted the yeast's own mevalonate pathway so that it made artemisinic acid, which is converted chemically into the drug; commercial production began in 2013. Other targets include biofuels, bulk chemicals and amino acids for animal feed.