AUTHOR=Xu Juan , Wang Yiyi , Zhang Yi , Xiong Kehui , Yan Xiaoyun , Ruan Shiyu , Wu Xueqian 

TITLE=Identification of a Novel Metabolic Target for Bioactive Triterpenoids Biosynthesis in Ganoderma lucidum

JOURNAL=Frontiers in Microbiology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2022.878110

DOI=10.3389/fmicb.2022.878110

ISSN=1664-302X

ABSTRACT=<p>Triterpenoids are crucial active ingredients of <italic>Ganoderma lucidum</italic> (<italic>G. lucidum</italic>) with various health benefits. Yet the low biosynthesis greatly restricts their industrial applications, novel metabolic engineering strategies are needed to further enhance <italic>Ganoderma</italic> triterpenoids production. Transcription factors play vital roles in the metabolic regulation of terpenoids, which are still scarce to study in <italic>G. lucidum</italic>. Herein, a transcription factor <italic>GlbHLH5</italic> (GenBank No. <ext-link ext-link-type="DDBJ/EMBL/GenBank" xlink:href="MZ436906.1" xmlns:xlink="http://www.w3.org/1999/xlink">MZ436906.1</ext-link>) potential for metabolic regulation of <italic>Ganoderma</italic> triterpenes was identified for the first time. MeJA could increase <italic>Ganoderma</italic> triterpenoids biosynthesis, and <italic>GlbHLH5</italic> significantly responded to MeJA induction, suggesting <italic>GlbHLH5</italic> is a new target for <italic>Ganoderma</italic> triterpenoids overproduction. The regulatory effect of the newly identified target was further validated by homologous gene overexpression and silence in <italic>G. lucidum</italic>. It’s demonstrated that overexpression of <italic>GlbHLH5</italic> significantly increased triterpenoids accumulation and the key enzyme genes transcription in the biosynthetic pathway, while silencing it displayed the opposite effect, indicating <italic>GlbHLH5</italic> could positively regulate the triterpenoids biosynthesis by activating the synergistic expression of key enzyme genes in the biosynthetic pathway. Consequently, <italic>GlbHLH5</italic> was identified as a positive regulator and novel metabolic target for <italic>Ganoderma</italic> triterpenoids biosynthesis, it sheds new lights on the regulatory effect regulation and synthetic biology of <italic>Ganoderma</italic> triterpenoids.</p>