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Polyketide belongs to a family of abundant natural products typically produced by the filamentous soil bacteria  Streptomyces . Similar to the biosynthesis of most secondary metabolites produced in the  Streptomyces  species, polyketide compounds are synthesized through tight regulatory networks in the cell, and thus extremely low levels of polyketides are typically observed in wild-type strains. Although many  Streptomyces  polyketides and their derivatives have potential to be used as clinically important pharmaceutical drugs, traditional strain improvement strategies such as random recursive mutagenesis have long been practiced with little understanding of the molecular basis underlying enhanced polyketide production. Recently, identifying, understanding, and applying a novel polyketide regulatory system identified from various Omics approaches, has become an important tool for rational  Streptomyces  strain improvement. In this paper, DNA microarray-driven reverse engineering efforts for improving titers of polyketides are briefly summarized, primarily focusing on our recent results of identification and application of novel global regulatory genes such as  wblA , SCO1712, and SCO5426 in  Streptomyces  species. Sequential targeted gene manipulation involved in polyketide biosynthetic reguation synergistically provided an efficient and rational strategy for  Streptomyces  strain improvement. Moreover, the engineered regulation-optimized  Streptomyces  mutant strain was further used as a surrogate host for heterologous expression of polyketide pathway.

biomed research international

Identification and Biotechnological Application of Novel Regulatory Genes Involved in<i>Streptomyces</i>Polyketide Overproduction through Reverse Engineering Strategy

Identification and Biotechnological Application of Novel Regulatory Genes Involved inStreptomycesPolyketide Overproduction through Reverse Engineering Strategy