Abstract
Natural products (NPs) are critical sources of drug molecules for decades. About two-thirds of natural antibiotics are produced by Streptomyces. Streptomyces have a large number of secondary metabolite biosynthetic gene clusters (SM-BGCs) that may encode NPs. However, most of these BGCs are silent under standard laboratory conditions. Hence, activation of these silent BGCs is essential to current natural products discovery research. In this review, we described the commonly used strategies for silent BGC activation in Streptomyces from two aspects. One focused on the strategies applied in heterologous host, including methods to clone and reconstruct BGCs along with advances in chassis engineering; the other focused on methods applied in native host which includes engineering of promoters, regulatory factors, and ribosomes. With the metabolic network being elucidated more comprehensively and methods optimized more high-thoroughly, the discovery of NPs will be greatly accelerated.
Highlights
Natural products (NPs) are major sources of drug molecules, including antibiotic, anticancer, antifungal, antiparasitic, and immunosuppressive compounds
In addition to the methods mentioned in this review, the silent biosynthetic gene clusters (BGCs) can be activated by changing the culture conditions
In 2019, a review discussed the use of microbial culture techniques to expand the range of NPs available in the laboratory in recent years, mainly including methods such as adding physical scaffolds, adding small molecule elicitors, and co-cultivating with another microorganism (Tomm et al, 2019)
Summary
Natural products (NPs) are major sources of drug molecules, including antibiotic, anticancer, antifungal, antiparasitic, and immunosuppressive compounds. Compared to expressions in native hosts, employ genomic library constructed by cosmid, fosmid, FIGURE 1 | Overview of strategies for silent BGCs activation.
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