1.Three new polyketides from vasR2 gene over-expressed mutant strain of Verrucosispora sp. NS0172.
Li-Ping DAI ; Wen LI ; Hao-Xin WANG ; Chun-Hua LU
Chinese Journal of Natural Medicines (English Ed.) 2021;19(7):536-539
Over-expression of the pathway specific positive regulator gene is an effective way to activate silent gene cluster. In the curret study, the SARP family regulatory gene, vasR2, was over-expressed in strain Verrucosispora sp. NS0172 and the cryptic gene cluster responsible for the biosynthesis of pentaketide ansamycin was partially activated. Two tetraketides (1 and 2) and a triketide (3) ansamycins, together with five known compounds (4-8), were isolated and elucidated from strain NS0172OEvasR2. Their NMR data were completely assigned by analysis of their HR-ESI-MS and
Micromonosporaceae/metabolism*
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Multigene Family
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Polyketides/metabolism*
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Rifabutin/metabolism*
2.Heterologous production of bioactive xenoacremone analogs in Aspergillus nidulans.
Zhiguo LIU ; Wei LI ; Peng ZHANG ; Yi SUN ; Wen-Bing YIN
Chinese Journal of Natural Medicines (English Ed.) 2023;21(6):436-442
Tyrosine-decahydrofluorene derivatives are a class of hybrid compounds that integrate the properties of polyketides and nonribosomal peptides. These compounds feature a [6.5.6] tricarbocyclic core and a para-cyclophane ether moiety in their structures and exhibit anti-tumor and anti-microbial activities. In this study, we constructed the biosynthetic pathway of xenoacremones from Xenoacremonium sinensis ML-31 in the Aspergillus nidulans host, resulting in the identification of four novel tyrosine-decahydrofluorene analogs, xenoacremones I-L (1-4), along with two known analogs, xenoacremones A and B. Remarkably, compounds 3 and 4 contained a 12-membered para-cyclophane ring system, which is unprecedented among tyrosine-decahydrofluorene analogs in X. sinensis. The successful reconstruction of the biosynthetic pathway and the discovery of novel analogs demonstrate the utility of heterologous expression strategy for the generation of structurally diverse natural products with potential biological activities.
Aspergillus nidulans/metabolism*
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Biological Products/metabolism*
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Polyketides/metabolism*
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Peptides/metabolism*
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Biosynthetic Pathways
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Multigene Family
3.The recent advances in developing gene editing and expression tools and the synthesis of natural products in Yarrowia lipolytica.
Jinhong ZHANG ; Zhiyong CUI ; Qingsheng QI ; Jin HOU
Chinese Journal of Biotechnology 2022;38(2):478-505
Yarrowia lipolytica, as an important oleaginous yeast, has been widely used in metabolic engineering. Y. lipolytica is considered as an ideal host for the production of natural products such as terpenes, polyketides and flavonoids, due to its ability to utilize a variety of hydrophobic substrates, high stress tolerance to acid and salt, high flux of tricarboxylic acid cycle and the ability in providing abundant the common precursor acetyl-CoA. Recently, more and more tools for genetic editing, gene expression and regulation has been developed in Y. lipolytica, which facilitate the metabolic engineering of Y. lipolytica for bio-manufacturing. In this review, we summarized the recent progresses in developing gene expression and natural product synthesis in Y. lipolytica, and also discussed the challenges and possible solutions in heterologous synthesis of natural products in this yeast.
Biological Products/metabolism*
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Gene Editing
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Metabolic Engineering
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Polyketides/metabolism*
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Yarrowia/metabolism*