Mechanism-Guided Design of Highly Efficient Protein Secretion and Lipid Conversion for Biomanufacturing and Biorefining

Advanced Science
Shangxian XieJoshua S Yuan

Abstract

Bacterial protein secretion represents a significant challenge in biotechnology, which is essential for the cost-effective production of therapeutics, enzymes, and other functional proteins. Here, it is demonstrated that proteomics-guided engineering of transcription, translation, secretion, and folding of ligninolytic laccase balances the process, minimizes the toxicity, and enables efficient heterologous secretion with a total protein yield of 13.7 g L-1. The secretory laccase complements the biochemical limits on lignin depolymerization well in Rhodococcus opacus PD630. Further proteomics analysis reveals the mechanisms for the oleaginous phenotype of R. opacus PD630, where a distinct multiunit fatty acid synthase I drives the carbon partition to storage lipid. The discovery guides the design of efficient lipid conversion from lignin and carbohydrate. The proteomics-guided integration of laccase-secretion and lipid production modules enables a high titer in converting lignin-enriched biorefinery waste to lipid. The fundamental mechanisms, engineering components, and design principle can empower transformative platforms for biomanufacturing and biorefining.

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Citations

Dec 21, 2019·Applied Microbiology and Biotechnology·Song JiaoZhongyao Shen
Feb 6, 2021·Critical Reviews in Biotechnology·Hui LiuLiming Liu
Jul 5, 2019·Metabolic Engineering·Garrett W RoellYinjie J Tang
May 11, 2020·Current Opinion in Chemical Biology·Kirsten Davis, Tae Seok Moon
Mar 14, 2021·Trends in Biotechnology·Allison L YaguchiMark A Blenner
Apr 1, 2021·ACS Synthetic Biology·Drew M DeLorenzoTae Seok Moon
Apr 7, 2021·Biotechnology Advances·Youxiang Liang, Huimin Yu
Jul 15, 2021·ChemSusChem·Cheng HuJoshua S Yuan
Aug 28, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Héctor M AlvarezMaría S Villalba
Aug 26, 2021·Synthetic and Systems Biotechnology·Youxiang LiangHuimin Yu

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Methods Mentioned

BETA
protein folding
Assay
Protein Assay

Software Mentioned

GenScript
TopSpin
MestreNova

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