Mechanism-Guided Design of Highly Efficient Protein Secretion and Lipid Conversion for Biomanufacturing and Biorefining. Academic Article uri icon


  • 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.

published proceedings

  • Adv Sci (Weinh)

author list (cited authors)

  • Xie, S., Sun, S. u., Lin, F., Li, M., Pu, Y., Cheng, Y., ... Yuan, J. S.

citation count

  • 38

complete list of authors

  • Xie, Shangxian||Sun, Su||Lin, Furong||Li, Muzi||Pu, Yunqiao||Cheng, Yanbing||Xu, Bing||Liu, Zhihua||da Costa Sousa, Leonardo||Dale, Bruce E||Ragauskas, Arthur J||Dai, Susie Y||Yuan, Joshua S

publication date

  • July 2019