GO:0031375 type II fatty acid synthase complex

[gocentral]

GO:0031375 has been made obsolete as: 'Type II refers to the type of fatty acid synthase. Type I is in a comlex, type II is not.'

However there are bacterial type II FAS elongation systems, which exists as a complex in the cytosol, see PMID: 12023885 and PMID: 11544358

"The type I FAS enzymes can have all of the active sites present in a single protein (as in mammals and mycobacteria) or split between two interacting proteins (as in fungi and Corynebacterium ammoniagenes). In contrast, each enzymatic activity is found as a discrete protein in type II systems. The differences in active site organization and the predominance of type II FAS systems in bacteria make the enzymes of this pathway attractive targets for antibacterials" PMID: 11544358

Reported by: edimmer

Original Ticket: geneontology/ontology-requests/8051

[gocentral]

The comments on the SF item for which GO:0031375 was obsoleted suggest that they took bacteria into account, and that the bacterial enzymes don't form a protein complex:

https://sourceforge.net/tracker/?func=detail&aid=3000204&group\_id=36855&atid=440764

But I don't know if that's still current thinking ...

Harold, can you take another look, or otherwise reassure everyone?

thanks! m

Original comment by: mah11

[gocentral]

• assigned_to: nobody --> hjdrabkin

Original comment by: mah11

[gocentral]

I'll ask Dianna to take a quck look also.

Original comment by: hdrabkin

[gocentral]

I read these two papers rather quickly, and I'm not even remotely and expert in mycobacteria, but I don't see how either of them provide evidence for a "type II FAS complex". As with a lot of papers on fatty acid synthases, people are a bit sloppy about the language and refer to FAS-I and FAS-II as though they are single entities, but they're referring to systems, not complexes.

I almost just quoted that same quote back, because I think it states the situation clearly. I don't see how it supports the creation of a type II complex. To restate what they said, "type I" and "type II" refer to whether the system is found in a complex (type I) or in a series of discrete proteins (type II). There are some bacterial systems that are in complexes, and by definition these are referred to as Type. You can even have both systems in a single organism, if you've got redundant or parallel systems. This has been well-characterized in mycobacteria, which have some funky fatty acids, relative to the rest of biology.

The word "discrete" in that quote is a bit open to interpretation, and when I suggested that the "Type I fatty acid complex" be obsoleted, I did a lot of reading trying to figure out if by "discrete" (the term people usually use), they mean just that the activities are discrete or that the proteins are discrete. I can't remember the exact references, but I do remember eventually finding papers that describe the FAS-II proteins as "disassociated" which is a bit clearer. Meaning that the proteins, and their discrete catalytic activities, function as separate entities.

This review goes on to talk about the different inhibitors and the complexes that they form with some of the members of type II Fatty acid synthase systems.

The other paper is a characterization of KasA, but doesn't actually show it in complex with any other FAS-II components, does it? It says that it's a functional link between the two systems (this mycobacterium has both FAS-I and FAS-II) and an "integral part of the mycobacterial type II FAS elongation system." Note the correct use of the word "system".

This paper talks a lot about KasA in complex with cerulinin (an inhibitor). It also references another paper that characterized a complex between KasA, INH and AcpM, but INH is an inhibitor, not a component of the system . From a quick read of that paper, it isn't clear to me if they even asked the question of whether or not these proteins form a complex in the absence of the inhibitor.

So, like I said, I don't see how these papers argue for a FAS-I complex, but again, I might be missing or misunderstanding something! Please point it out if I did.

Thanks,

-Dianna

P.S. The review does mention the ACC complex. In a reversal of the situation with the rest of the fatty acid synthesis enzymatic activities, bacteria have a multi-protein ACC complex where eukaryotes (well, at least mammals and S. cerevisiae) have a single, discrete protein. As far as I know, the ACC activity is never found in complex with the other enzymes of fatty acid synthesis. Also, the ACC complex looks to be properly represented in GO GO:0009317).

Original comment by: diannafisk

[gocentral]

Sorry, typo. I meant to say, "There are some bacterial systems that are in complexes, and by definition these are referred to as Type I".

-Dianna

Original comment by: diannafisk

[gocentral]

But the active forms of ALL of them appear to be complexes in vivo. In E. coli, seven different genes encode seven polypeptides that assemble into a complex. In Saccharomyces, one gene encodes a polypeptide with three of these activities, a second gene encodes a polypeptide with the other four, and the in vivo form of the enzyme is a dodecamer containing six of each polypeptide. In humans, one gene encodes one polypeptide with all severn activitiwes, but in vivo it dimerizes. Stryer's Biochemistry, 4th edition, summarizes nicely (and accurately as far as I know) at pp. 617-618.

So it looks like there is a distinction between systems that encode everything in one gene (human, and what else?) and ones that encode it in more than one gene (the rest), but that may be the only distinction.

Peter

Original comment by: deustp01

[gocentral]

Peter, can you dig up a reference for the complex formation in E. coli? That would be what we need to make this term. From the reviews I read, it sounded like they acted as discrete entities, rather than as a complex, but I only read reviews.

Thanks,

-Dianna

Original comment by: diannafisk

[gocentral]

It looks like I cannot dig up a reference that demonstrates the existence of a stable multiprotein bacterial FAS complex. Instead, I find that Goldman et al (1963 - PMID:13948777) and Lennarz et al. (1962 - PMID: 16590950) partly purified "systems" from E. coli that could carry out all of the steps of fatty acid synthesis. Wakil et al. (1964 - PMID: 14192647) separated enzymes that catalyzed individual steps of the overall synthetic process from the Lennarz "system". That doesn't prove that the E. coli proteins do not normally associate with one another to form a stable noncovalent complex, but none of these investigators (nor anyone since as far as I know) has pursued this point. There is extensive work on the close interactions between acyl carrier protein and each of the other components of the "system", needed for successful long-chain fatty acid synthesis but, again, that's not proof of the formation of stable complexes.

Peter

Original comment by: deustp01

[gocentral]

It sounds like there's no evidence for a stable type II complex, so we'll close this SF item. Go ahead and open it if new evidence comes to light.

Thanks! GOEd

Original comment by: rebeccafoulger

[gocentral]

• status: open --> closed-rejected

Original comment by: rebeccafoulger