Comparative transcriptome analysis of the fungus Gibberella zeae transforming lithocholic acid into ursodeoxycholic acid
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ORIGINAL RESEARCH PAPER
Comparative transcriptome analysis of the fungus Gibberella zeae transforming lithocholic acid into ursodeoxycholic acid Biling Yang . Renfen Zha . Wenyan Zhao . Daoyong Gong . Xinhua Meng . Zhi Zhang . Liancai Zhu . Na Qi . Bochu Wang
Received: 7 April 2020 / Accepted: 4 November 2020 Ó Springer Nature B.V. 2020
Abstract The comparative transcriptome analysis of the fungus Gibberella zeae which could efficiently catalyze the 7b-hydroxylation of LCA to produce UDCA was performed with LCA induction. This is the first time to report the comparative transcriptome of fungus under LCA treatment. Totally, 1364 differentially expressed genes including 770 up-regulated and 594 down-regulated genes were identified. In the 770 up-regulated genes, 12 genes with the function of hydroxylation were picked out by application of function screening, which were annotated as CYP450 or hydroxylase. Moreover, the qRT-PCR results of five up-regulated CYP450-like genes
confirmed the credibility of RNA-Seq further. These results provide valuable information for the discovery of novel enzyme producing clinical drug UDCA from butchery byproduct LCA, and also might indicate some clues for the detoxification process of LCA in humans. Keywords Comparative transcriptome CYP450 Hydroxylase Hydroxylation Lithocholic acid Ursodeoxycholic acid
Introduction Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10529-020-03048-z) contains supplementary material, which is available to authorized users. B. Yang R. Zha W. Zhao D. Gong X. Meng Z. Zhang L. Zhu (&) N. Qi (&) B. Wang (&) Key Laboratory of Biorheological Science and Technology (Chongqing University), Ministry of Education, College of Bioengineering, Chongqing University, Chongqing 400030, China e-mail: [email protected] N. Qi e-mail: [email protected] B. Wang e-mail: [email protected] R. Zha e-mail: [email protected]
Ursodeoxycholic acid (UDCA) is the clinical first-line drug to treat primary biliary cirrhosis (PBC) approved by FDA in 1997, and has also been the only drug for PBC until the appearance of obeticholic acid in 2016 (Gossard and Lindor 2019). Meanwhile, UDCA is also the main ingredient of the famous Chinese traditional medicine bear gall power which has been used in kinds of diseases for thousands of years. The enzymatic synthesis of UDCA from the cheap butchery byproduct chenodeoxycholic acid (CDCA) has been studied extensively for many years (Ji et al. 2016). However, in tons of butchery wastes, many bile acids still could not be utilized and were finally discarded, such as lithocholic acid (LCA). The enzymatic 7b-hydroxylation of useless LCA is a feasible
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strategy to produce valuable UDCA (Scheme 1). Besides, LCA is an important secondary bile acid with weak toxicity, whose accumulation is the main factor of liver injury in cholestasis and also risk factors for colonic inflammation and cancer (Gossard and Lindor
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