Identification of a critical determinant that enables efficient fatty acid synthesis in oleaginous fungi.

Haiqin Chen,Yong Q Chen,Hongchao Wang,Lei Wang,Zhennan Gu,Wei Chen,Liming Liu,Guangfei Hao,Hao Zhang

doi:10.1038/srep11247

Abstract

Microorganisms are valuable resources for lipid production. What makes one microbe but not the other able to efficiently synthesize and accumulate lipids is poorly understood. In the present study, global gene expression prior to and after the onset of lipogenesis was determined by transcriptomics using the oleaginous fungus Mortierella alpina as a model system. A core of 23 lipogenesis associated genes was identified and their expression patterns shared a high similarity among oleaginous microbes Chlamydomonas reinhardtii, Mucor circinelloides and Rhizopus oryzae but was dissimilar to the non-oleaginous Aspergillus nidulans. Unexpectedly, Glucose-6-phosphate dehydrogenase (G6PD) and 6-phosphogluconate dehydrogenase (PGD) in the pentose phosphate pathway (PPP) were found to be the NADPH producers responding to lipogenesis in the oleaginous microbes. Their role in lipogenesis was confirmed by a knockdown experiment. Our results demonstrate, for the first time, that the PPP plays a significant role during fungal lipogenesis. Up-regulation of NADPH production by the PPP, especially G6PD, may be one of the critical determinants that enables efficiently fatty acid synthesis in oleaginous microbes.

Highlights

We compared the transcriptomes prior to and after the onset of lipogenesis and examined the coordinated regulation of genes involved in carbon flux and NADPH production using M. alpina as a model system, in order to understand better the mechanisms underlying the efficient lipid synthesis and accumulation in oleaginous microbes
Protein and nucleic acid synthesis were severely limited, and cell multiplication stopped (Fig. 1); glucose continued to be assimilated and the cells switched to lipid accumulation (Fig. 1)
We found that the PPP is the NADPH producer responding to lipogenesis in M. alpina

Summary

Introduction

The cytosolic malic enzyme (ME, EC 1.1.1.40) was considered to be the sole provider of NADPH for fatty acid synthesis in oleaginous microbes[8,9,10]. This unique role of ME in microbial lipid synthesis was challenged[11,12] and this enzyme is recognized as one of the sources of NADPH for fatty acid synthesis[13,14].

Methods

Results

Conclusion