Development of a cyanobacterial heterologous polyketide production platform.

ROULET J, TATON A, GOLDEN JW, ARABOLAZA A, BURKART MD, GRAMAJO H; HUGO GRAMAJO

METABOLIC ENGINEERING

ACADEMIC PRESS INC ELSEVIER SCIENCE

Lugar: Amsterdam; Año: 2018

1096-7176

The development of new heterologous hosts for polyketides production represents an excellent opportunity toexpand the genomic, physiological, and biochemical backgrounds that better fit the sustainable production ofthese valuable molecules. Cyanobacteria are particularly attractive for the production of natural compoundsbecause they have minimal nutritional demands and several strains have well established genetic tools. Using themodel strain Synechococcus elongatus, a generic platform was developed for the heterologous production ofpolyketide synthase (PKS)-derived compounds. The versatility of this system is based on interchangeablemodules harboring promiscuous enzymes for PKS activation and the production of PKS extender units, as well asinducible circuits for a regulated expression of the PKS biosynthetic gene cluster. To assess the capability of thisplatform, we expressed the mycobacterial PKS-based mycocerosic biosynthetic pathway to produce multimethylbranchedesters (MBE). This work is a foundational step forward for the production of high value polyketides in aphotosynthetic microorganism.