Co-existence of type I fatty acid synthase and polyketide synthase metabolons in Aurantiochytrium SW1 and their implications for lipid biosynthesis

Shuwahida Shuib; Mohamed Yusuf Mohamed Nazir; Izyanti Ibrahim; Yuanda Song; Colin Ratledge; Aidil Abdul Hamid

doi:10.1016/j.bbalip.2022.159224

Co-existence of type I fatty acid synthase and polyketide synthase metabolons in Aurantiochytrium SW1 and their implications for lipid biosynthesis

Biochim Biophys Acta Mol Cell Biol Lipids. 2022 Dec;1867(12):159224. doi: 10.1016/j.bbalip.2022.159224. Epub 2022 Aug 22.

Authors

Shuwahida Shuib¹, Mohamed Yusuf Mohamed Nazir², Izyanti Ibrahim³, Yuanda Song⁴, Colin Ratledge⁵, Aidil Abdul Hamid⁶

Affiliations

¹ Department of Biological Sciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor, Malaysia; Autoimmune Unit, Allergy and Immunology Research Centre, Institute for Medical Research (IMR), National Institute of Health (NIH) Malaysia, No. 1, Jalan Setia Murni U13/52, Bandar Setia Alam, 40170 Shah Alam, Selangor, Malaysia.
² Department of Food Sciences, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor, Malaysia; Innovation Centre for Confectionery Technology (MANIS), Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor, Malaysia.
³ Department of Biological Sciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor, Malaysia.
⁴ Colin Ratledge Center for Microbial Lipids, School of Agriculture Engineering and Food Sciences, Shandong University of Technology, 266 Xincun Rd., Zibo, Shandong, PR China.
⁵ Department of Biological Sciences, University of Hull, Kingston upon Hull HU6 7RX, United Kingdom.
⁶ Department of Biological Sciences and Biotechnology, Faculty of Science and Technology, Universiti Kebangsaan Malaysia, 43600 Bangi, Selangor, Malaysia. Electronic address: aidilmikrob@gmail.com.

PMID: 36007759
DOI: 10.1016/j.bbalip.2022.159224

Abstract

The key enzymes of lipid biosynthesis in oleaginous filamentous fungi exist as metabolons. However, the existence of a similar organization in other groups of oleaginous microorganisms is still unknown. In this study, we confirmed the occurrence of two separate and distinct lipogenic metabolons in a thraustochytrid, Aurantiochytrium SW1. These involve the Type I Fatty Acid Synthase (FAS) pathway, consisting of six enzymes: fatty acid synthase, malic enzyme (ME), ATP: citrate lyase (ACL), acetyl-CoA carboxylase (ACC), malate dehydrogenase (MD) and pyruvate carboxylase (PC), and the Polyketide Synthase-like (PKS) pathway, consisting of PKS subunits a, b, c, glucose-6-phosphate dehydrogenase (G6PDH) 6-phosphogluconate dehydrogenase (6PGDH), ACL and ACC. This suggests that the NADPH requirement for the FAS pathway is primarily generated and channelled by ME whereas G6PDH and 6PGDH fulfil this role for the PKS pathway. Diminished biosynthesis of palmitic acid (16:0), docosahexaenoic acid (22:6 n-3, DHA) and docosapentaenoic acid (22:5 n-6, DPA) correlated with the dissociation of their respective metabolons thereby suggesting that regulation of the pathways is achieved through the formation and dissociation of the metabolons.

Keywords: Fatty acid synthase; Lipogenic enzymes; Metabolon; Polyketide synthase; Thraustochytrids.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acetyl-CoA Carboxylase
Adenosine Triphosphate
Docosahexaenoic Acids
Fatty Acid Synthases / metabolism
Glucosephosphate Dehydrogenase
Malate Dehydrogenase* / metabolism
NADP
Palmitic Acid
Phosphogluconate Dehydrogenase
Polyketide Synthases
Pyruvate Carboxylase
Stramenopiles* / metabolism

Substances

Docosahexaenoic Acids
Palmitic Acid
NADP
Polyketide Synthases
Adenosine Triphosphate
Malate Dehydrogenase
Phosphogluconate Dehydrogenase
Glucosephosphate Dehydrogenase
Fatty Acid Synthases
Pyruvate Carboxylase
Acetyl-CoA Carboxylase