Strategies for Enhancing the Yield of the Potent Insecticide Spinosad in Actinomycetes

Abstract

Spinosad is a potent insecticide that exhibits an excellent environmental and mammalian profile. However, spinosad production in the original producer, Saccharopolyspora spinosa, is insufficient for the huge global demand. Great efforts have been exerted to improve the production of spinosad. Strategies for spinosad overproduction in actinomycetes are reviewed in this article, including metabolic engineering of the precursor and spinosyn biosynthetic pathway, introduction of regulatory genes, genome-scale metabolic model-guided engineering, mutagenesis, genome shuffling, fermentation process optimization, omics analysis, and the heterologous biosynthesis of spinosad in other actinomycetes. Furthermore, highly productive industrial strains should be used as heterologous hosts for enhancing spinosad biosynthesis in the future. To accelerate the engineering process, the CRISPR/Cas9 system should be established in Sa. spinosa for large-scale genome editing. Notably, the regulatory mechanism of spinosad biosynthesis remains unclear. Thus, the combining multi-omics analysis with high-throughput screening of chemical elicitors would be a promising approach in characterizing the regulatory and signal transduction mechanisms and improving spinosad production in Sa. Spinosa.

Effect of the TetR family transcriptional regulator Sp1418 on the global metabolic network of Saccharopolyspora pogona

“…The structure and biosynthesis of spinosyn analogues have been clearly described [4,33], and studies on the transformation of its gene clusters and the improvement of heterologous expression have been studied [7,34,35]; however, the metabolic situation in vivo is complex, and any slight metabolic disturbance will lead to complex changes, which may produce unintended consequences [11]. Therefore, the analysis of the genome characteristics of S. pogona and related regulatory proteins may help to understand their gene expression preferences.…”

rpoB and efp are stable candidate reference genes for quantitative real-time PCR analysis in Saccharopolyspora spinosa

“…Spinosad (spinosyn A and spinosyn D) is a member of polyketide-derived macrolide insecticide with high effectiveness and broad-spectrum insecticidal activity [1]. Taking the advantages of low mammalian and avian toxicity and low environmental impact, spinosad was awarded 'The Presidential Green Chemistry Challenge (U.S.A.)' three times and was permitted to be used on organic food by the European Union, leading to a high market demand [2][3][4].…”

Marker‐Free System Using Ribosomal Promoters Enhanced Xylose/Glucose Isomerase Production in Streptomyces rubiginosus

“…Streptomycetes are production hosts for approximately two‐thirds of all natural antibiotics, industrial enzymes, and pharmaceutically relevant compounds . One of the key advantages of these bacteria is that they are the most abundant organisms with a twin‐arginine translocation (TAT) secretion pathway for protein expression .…”

“…Streptomycetes are production hosts for approximately twothirds of all natural antibiotics, industrial enzymes, and pharmaceutically relevant compounds. [14][15][16] One of the key advantages of these bacteria is that they are the most abundant organisms with a twin-arginine translocation (TAT) secretion pathway for protein expression. [17] However, compared to other typical microbial cell factories, such as E. coli, Bacillus, Aspergillus, Trichoderma, and yeast, [18] there are few reports on the potential of Streptomyces in industrial protein production.…”