Combining metabolic engineering and process optimization to improve production and secretion of fatty acids

Ledesma-Amaro, Rodrigo; Dulermo, Rémi; Niehus, Xochitl

doi:10.1016/j.ymben.2016.06.004

Cited by 146 publications

(103 citation statements)

References 56 publications

(72 reference statements)

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“…From analysis of other bacteria, lipid secretion often occurs by export of free fatty acids or outer membrane vesicle (OMV) formation (50–52). For the HL mutants with the highest levels of secreted lipid (HLM01, HLM02, and HLM05), lipid phosphorus assays indicated the presence of extracellular phospholipid (Fig.…”

Section: Discussionmentioning

confidence: 99%

Mutations That Alter the Bacterial Cell Envelope Increase Lipid Production

Lemmer

Zhang

Langer

et al. 2017

mBio

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Lipids from microbes offer a promising source of renewable alternatives to petroleum-derived compounds. In particular, oleaginous microbes are of interest because they accumulate a large fraction of their biomass as lipids. In this study, we analyzed genetic changes that alter lipid accumulation in Rhodobacter sphaeroides. By screening an R. sphaeroides Tn5 mutant library for insertions that increased fatty acid content, we identified 10 high-lipid (HL) mutants for further characterization. These HL mutants exhibited increased sensitivity to drugs that target the bacterial cell envelope and changes in shape, and some had the ability to secrete lipids, with two HL mutants accumulating ~60% of their total lipids extracellularly. When one of the highest-lipid-secreting strains was grown in a fed-batch bioreactor, its lipid content was comparable to that of oleaginous microbes, with the majority of the lipids secreted into the medium. Based on the properties of these HL mutants, we conclude that alterations of the cell envelope are a previously unreported approach to increase microbial lipid production. We also propose that this approach may be combined with knowledge about biosynthetic pathways, in this or other microbes, to increase production of lipids and other chemicals.

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Section: Discussionmentioning

confidence: 99%

Mutations That Alter the Bacterial Cell Envelope Increase Lipid Production

Lemmer

Zhang

Langer

et al. 2017

mBio

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“…Yeasts also contain fatty acid transporters; these are mainly homologues of mammalian FAT1 [113][114][115]. It is of particular interest that the Fat1p homologue in the oleaginous yeast Yarrowia lipolytica is involved in the export of fatty acids [116][117][118][119].…”

Section: Fatty Acidsmentioning

confidence: 99%

Control of metabolite efflux in microbial cell factories: current advances and future prospects

Kell¹

2018

Preprint

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The yield and ease of purification of biotechnological products are typically greatly enhanced if they can be secreted into the external medium. Although not universally appreciated, however, small molecule biotechnological products do not ‘float across’ the phospholipid bilayer portion of biological membranes, and thus they need transporters to assist their passage into the extramembrane and extracellular spaces. Some of these transporters may be reversible, equilibrative transporters that might more normally be used for uptake, while others may have an efflux directionality imposed on them via suitable energy coupling mechanisms. Despite the energetic costs of small molecule synthesis, natural evolution does in fact provide a number of mechanisms by which the secretion of such products can actually enhance fitness. Where available these provide useful starting points, and assaying for such activities is crucial. In particular, in a systems biology approach, we first need to identify such/suitable activities before we can seek to increase them. They may then be improved through promoter engineering, via manipulation of control elements, or by directed evolution of the transporter proteins themselves. Modern methods of synthetic biology provide enormous opportunities for all kinds of efflux transporter engineering; they are just beginning to be realised.

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“…Due to the vast array of engineering techniques currently available, the recombinant DNA technology was the main approach followed so far for obtaining lipid-overproducing yeasts; in this contest, the species Yarrowia lipolytica was the most studied oleaginous yeast [1, 19, 28–34]. However, an alternative approach can be offered by yeast worldwide diversity as source of novel oleaginous yeasts [4, 11, 12].…”

Section: Introductionmentioning

confidence: 99%

Study of Holtermanniella wattica, Leucosporidium creatinivorum, Naganishia adeliensis, Solicoccozyma aeria, and Solicoccozyma terricola for their lipogenic aptitude from different carbon sources

Filippucci

Tasselli

Scardua

et al. 2016

Biotechnol Biofuels

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BackgroundThe ability of some microorganisms to accumulate lipids is well known; however, only recently the number of studies on microbial lipid biosynthesis for obtaining oleochemical products, namely biofuels and some building blocks for chemistry, is rapidly and spectacularly increased. Since 1990s, some oleaginous yeasts were studied for their ability to accumulate lipids up to 60–70% of their dry weight. Due to the vast array of engineering techniques currently available, the recombinant DNA technology was the main approach followed so far for obtaining lipid-overproducing yeasts, mainly belonging to the Yarrowia lipolytica. However, an alternative approach can be offered by worldwide diversity as source of novel oleaginous yeasts. Lipogenic aptitude of a number of yeast strains has been reviewed, but many of these studies utilized a limited number of species and/or different culture conditions that make impossible the comparison of different results. Accordingly, the lipogenic aptitude inside the yeast world is still far from being fully explored, and finding new oleaginous yeast species can acquire a strategic importance.Results Holtermanniella wattica, Leucosporidium creatinivorum, Naganishia adeliensis, Solicoccozyma aeria, and Solicoccozyma terricola strains were selected as a result of a large-scale screening on 706 yeasts (both Ascomycota and Basidiomycota). Lipid yields and fatty acid profiles of selected strains were evaluated at 20 and 25 °C on glucose, and on glycerol, xylose, galactose, sucrose, maltose, and cellobiose. A variable fatty acid profile was observed in dependence of both temperature and different carbon sources. On the whole, L. creatinivorum exhibited the highest performances: total lipid yield (YL) >7 g/l on glucose and glycerol, % of intracellular lipids on cell biomass (YL/DW) >70% at 20 °C on glucose, lipid coefficient (YL/Glu) around 20% on glucose, and daily productivity (YL/d) on glucose and sucrose >1.6 g/(l*d).ConclusionsThis study provides some meaningful information about the lipogenic ability of some yeast species. Variable lipid yields and fatty acid profiles were observed in dependence of both temperature and different carbon sources. L. creatinivorum exhibited the highest lipogenic performances.Electronic supplementary materialThe online version of this article (doi:10.1186/s13068-016-0672-1) contains supplementary material, which is available to authorized users.

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Combining metabolic engineering and process optimization to improve production and secretion of fatty acids

Cited by 146 publications

References 56 publications

Mutations That Alter the Bacterial Cell Envelope Increase Lipid Production

Mutations That Alter the Bacterial Cell Envelope Increase Lipid Production

Control of metabolite efflux in microbial cell factories: current advances and future prospects

Study of Holtermanniella wattica, Leucosporidium creatinivorum, Naganishia adeliensis, Solicoccozyma aeria, and Solicoccozyma terricola for their lipogenic aptitude from different carbon sources

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