AI Article Synopsis

  • Advances in synthetic biology and metabolic engineering enable the creation of more efficient metabolic pathways in cell factories, bypassing the host's regulatory mechanisms.
  • The research involved replacing the native MEP pathway for isoprenoid biosynthesis in Rhodobacter sphaeroides with a heterologous mevalonate (MVA) pathway from a similar bacterium.
  • The engineered strain produced higher yields of sesquiterpenes than the control strain by expressing only the MVA pathway, demonstrating improved biosynthetic performance through this pathway substitution.

Article Abstract

Advances in synthetic biology and metabolic engineering have proven the potential of introducing metabolic by-passes within cell factories. These pathways can provide a more efficient alternative to endogenous counterparts due to their insensitivity to host's regulatory mechanisms. In this work, we replaced the endogenous essential 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway for isoprenoid biosynthesis in the industrially relevant bacterium Rhodobacter sphaeroides by an orthogonal metabolic route. The native 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway was successfully replaced by a heterologous mevalonate (MVA) pathway from a related bacterium. The functional replacement was confirmed by analysis of the reporter molecule amorpha-4,11-diene after cultivation with [4- C]glucose. The engineered R. sphaeroides strain relying exclusively on the MVA pathway was completely functional in conditions for sesquiterpene production and, upon increased expression of the MVA enzymes, it reached even higher sesquiterpene yields than the control strain coexpressing both MEP and MVA modules. This work represents an example where substitution of an essential biochemical pathway by an alternative, heterologous pathway leads to enhanced biosynthetic performance.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264872PMC
http://dx.doi.org/10.1111/1751-7915.13562DOI Listing

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