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A biological OR(XNOR) logic gate couples carbon source and transgene expression switching in a Komagatella phaffii (Pichia pastoris) strain co-producing process-enhancing lipase and a virus-like particle (VLP) vaccine

Bandyopadhyay, Sushobhan; Pavlika, Vasos; Bracewell, Daniel; Nesbeth, Darren; (2023) A biological OR(XNOR) logic gate couples carbon source and transgene expression switching in a Komagatella phaffii (Pichia pastoris) strain co-producing process-enhancing lipase and a virus-like particle (VLP) vaccine. ACS Synthetic Biology , 12 (3) pp. 657-663. 10.1021/acssynbio.2c00342. Green open access

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Abstract

We constructed a three-input biological logic gate: S OR (G XNOR M), where S is sorbitol, G is glycerol, and M is methanol, to optimize co-expression of two transgenes in Komagataella phaffii using batch-mode carbon source switching (CSS). K. phaffii was engineered to harbor transgenes encoding a Candida rugosa triacylglycerol lipase, which can enhance downstream processing by removing host cell lipids from homogenates, and the hepatitis B virus surface antigen (HBsAg), a protein that self-assembles into a virus-like particle (VLP) vaccine. Using the native alcohol oxidase 1 (PAOX1) and enolase 1 (PENO1) promoters to direct VLP vaccine and lipase expression, respectively, successfully provided an OR(XNOR) gate function with double-repression as the output. This logic gate functionality enabled use of CSS to ensure that approximately 80% of total VLP yield was accumulated before cells were burdened with lipase expression in 250 mL DasGip bioreactor cultivation.

Type: Article
Title: A biological OR(XNOR) logic gate couples carbon source and transgene expression switching in a Komagatella phaffii (Pichia pastoris) strain co-producing process-enhancing lipase and a virus-like particle (VLP) vaccine
Open access status: An open access version is available from UCL Discovery
DOI: 10.1021/acssynbio.2c00342
Publisher version: https://doi.org/10.1021/acssynbio.2c00342
Language: English
Additional information: Copyright © 2023 The Authors. Published under the Creative Commons CC BY public use license.
Keywords: Triacylglycerol lipase, logic gate, virus-like particle, vaccine, bioreactor, carbon source
UCL classification: UCL
UCL > Provost and Vice Provost Offices > UCL BEAMS
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science
UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Engineering Science > Dept of Biochemical Engineering
URI: https://discovery.ucl.ac.uk/id/eprint/10164604
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