Gate 1 — Capture vs. Degradation

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ENGINEERING SUCCESS · 02

GATE 01

Capture vs. Degradation

Our first major engineering decision was deciding what should happen to DEHP after our bacteria encountered it.

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THE QUESTION

Should we break DEHP down or capture it?

At first, degradation seemed like the obvious solution. If DEHP could be broken down, the original contaminant would disappear. But engineering a degradation pathway meant we also had to understand everything that pathway produced.

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Two ways forward.

01 INVESTIGATED

Degradation

Use enzymes to transform DEHP into smaller chemical compounds.

DEHP
MEHP
Byproducts
But what happens after DEHP is broken down?
02 SELECTED

Capture

Bind DEHP to the bacterial surface and remove the bacteria-containing material from the environment.

DEHP
LGG
Can the bacterium naturally capture enough DEHP?
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We tested the degradation route.

We investigated EstS1 and MphG1 as possible enzymes for breaking down DEHP. This gave us a way to explore whether degradation could provide a better endpoint than simply capturing the molecule.

A

EstS1

A candidate esterase investigated as part of our degradation strategy.

Candidate enzyme
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MEHP

Breaking DEHP wasn't the end.

One of the biggest problems with the degradation approach was the formation of MEHP.

Instead of simply making the original problem disappear, degradation could transform DEHP into another compound that we would then need to consider.

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New question

Are we actually solving the problem if we create another compound that still needs to be addressed?

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The pathway created more questions.

START DEHP
PRODUCT MEHP
QUESTION What remains?

Rather than creating a new chain of compounds that we would have to track and evaluate, we began looking more seriously at whether capture and removal could give us a cleaner endpoint.

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What if the bacterium did the work?

Instead of introducing another degradation pathway, we investigated the natural ability of our bacterial chassis, LGG, to interact with hydrophobic compounds.

This shifted our thinking. We did not necessarily need to engineer a complicated pathway if the bacterium could already provide a useful starting point for DEHP sequestration.

LGG
DEHP
DEHP
DEHP
DEHP

DEHP becomes associated with the bacterial surface

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CAPTURE REMOVE CAPTURE REMOVE

Capture and remove.

We chose to move forward with sequestration rather than degradation. By capturing DEHP instead of transforming it, we could focus our engineering efforts on binding the contaminant and physically removing it from the system.

But one question remained: what should do the capturing?

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Protein engineering vs. bacterial sequestration

We next explored whether we should engineer a protein specifically for DEHP binding—or let the bacterium itself do the work.

Enter Gate 2 → ```