Large-scale and cost-effective production of recombinant human serum albumin (rHSA) in transgenic Bombyx mori cocoons

Int J Biol Macromol. 2023 Aug 1:245:125527. doi: 10.1016/j.ijbiomac.2023.125527. Epub 2023 Jun 26.

Abstract

HSA is considered a versatile natural cargo carrier with multiple bio-functions and applications. However, insufficient supply of HSA has limited widespread use. Although various recombinant expression systems had been applied to produce the rHSA to overcome the limited resource, cost-effective and large scale production of rHSA remains a challenge. Herein, we provide a strategy for the large-scale and cost-effective production of rHSA in cocoons of transgenic silkworms, achieving a final 13.54 ± 1.34 g/kg of rHSA yield in cocoons. rHSA was efficiently synthesized and stable over the long-term in the cocoons at room temperature. Artificial control of silk crystal structure during silk spinning significantly facilitated rHSA extraction and purification, with 99.69 ± 0.33 % purity and a productivity of 8.06 ± 0.17 g rHSA from 1 kg cocoons. The rHSA had the same secondary structure to natural HSA, along with effective drug binding capacity, biocompatibility, and bio-safe. The rHSA was successfully evaluated as a potential substitute in serum-free cell culture. These findings suggest the silkworm bioreactor is promising for large-scale and cost-effective production of high quality rHSA to meet the increased worldwide demand.

Keywords: Human serum albumin; Recombinant expression; Silkworm.

MeSH terms

  • Animals
  • Animals, Genetically Modified / genetics
  • Bombyx* / genetics
  • Bombyx* / metabolism
  • Cost-Benefit Analysis
  • Humans
  • Recombinant Proteins / chemistry
  • Serum Albumin, Human* / chemistry
  • Silk / genetics
  • Silk / metabolism

Substances

  • Serum Albumin, Human
  • Recombinant Proteins
  • Silk