Augmenting the Calvin-Benson-Bassham cycle by a synthetic malyl-CoA-glycerate carbon fixation pathway

Nat Commun. 2018 May 22;9(1):2008. doi: 10.1038/s41467-018-04417-z.

Abstract

The Calvin-Benson-Bassham (CBB) cycle is presumably evolved for optimal synthesis of C3 sugars, but not for the production of C2 metabolite acetyl-CoA. The carbon loss in producing acetyl-CoA from decarboxylation of C3 sugar limits the maximum carbon yield of photosynthesis. Here we design a synthetic malyl-CoA-glycerate (MCG) pathway to augment the CBB cycle for efficient acetyl-CoA synthesis. This pathway converts a C3 metabolite to two acetyl-CoA by fixation of one additional CO2 equivalent, or assimilates glyoxylate, a photorespiration intermediate, to produce acetyl-CoA without net carbon loss. We first functionally demonstrate the design of the MCG pathway in vitro and in Escherichia coli. We then implement the pathway in a photosynthetic organism Synechococcus elongates PCC7942, and show that it increases the intracellular acetyl-CoA pool and enhances bicarbonate assimilation by roughly 2-fold. This work provides a strategy to improve carbon fixation efficiency in photosynthetic organisms.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetyl Coenzyme A / metabolism
  • Acyl Coenzyme A / metabolism*
  • Bacterial Proteins / genetics
  • Bacterial Proteins / metabolism
  • Carbon Dioxide / metabolism*
  • Escherichia coli / genetics*
  • Escherichia coli / metabolism
  • Glyceric Acids / metabolism*
  • Glyoxylates / metabolism
  • Metabolic Engineering / methods
  • Photosynthesis / genetics*
  • Synechococcus / genetics*
  • Synechococcus / metabolism
  • Transgenes

Substances

  • Acyl Coenzyme A
  • Bacterial Proteins
  • Glyceric Acids
  • Glyoxylates
  • Carbon Dioxide
  • malyl-coenzyme A
  • Acetyl Coenzyme A
  • glyoxylic acid