Ieodoglucomides A (1) and B (2), unique glycolipopeptides consisting of an amino acid, a new fatty acid, a succinic acid, and a sugar, were isolated from a Marine-derived bacterium Bacillus licheniformis. The absolute stereochemistry of 1 and 2 was determined by deploying coupling constants, Marfey's and Mosher's methods, and literature reviews. Compounds 1 and 2 displayed moderate in vitro antimicrobial activity. Furthermore, ieodoglucomide B (2) exhibited cytotoxic activity against lung cancer and stomach cancer cell lines with GI(50) values of 25.18 and 17.78 μg/mL, respectively.

Bacillus licheniformis, antimicrobial activity, ieodoglucomides, glycolipopeptides, cytotoxic activity

13C NMR data:
Linkage	Residue	C1	C2	C3	C4	C5	C6	C7	C8	C9	C10	C11	C12	C13	C14	C15	C16	C17
2,14,6	xXSuc	174.0	30.2	29.9	175.9
2,14	bDGlcp	104.2	75.5	78.1	71.9	75.1	65.2
2	Subst	176.3	36.9	27.0	29.9-30.9	29.9-30.9	29.9-30.9	29.9-30.9	29.9-30.9	29.9-30.9	29.9-30.9	29.9-30.9	26.6	32.2	85.6	32.3	18.3	18.7
	xLAla?	176.3	49.3	17.8


1H NMR data:
Linkage	Residue	H1	H2	H3	H4	H5	H6	H7	H8	H9	H10	H11	H12	H13	H14	H15	H16	H17
2,14,6	xXSuc	-	2.61	2.61	-
2,14	bDGlcp	4.29	3.18	3.33	3.28	3.40	4.18-4.44
2	Subst	-	2.22	1.61	1.29	1.29	1.29	1.29	1.29	1.29	1.29	1.29	1.29	1.46	3.42	1.87	0.93	0.93
	xLAla?	-	4.37	1.38


1H/13C HSQC data:
Linkage	Residue	C1/H1	C2/H2	C3/H3	C4/H4	C5/H5	C6/H6	C7/H7	C8/H8	C9/H9	C10/H10	C11/H11	C12/H12	C13/H13	C14/H14	C15/H15	C16/H16	C17/H17
2,14,6	xXSuc		30.2/2.61	29.9/2.61	
2,14	bDGlcp	104.2/4.29	75.5/3.18	78.1/3.33	71.9/3.28	75.1/3.40	65.2/4.18-4.44
2	Subst		36.9/2.22	27.0/1.61	29.9-30.9/1.29	29.9-30.9/1.29	29.9-30.9/1.29	29.9-30.9/1.29	29.9-30.9/1.29	29.9-30.9/1.29	29.9-30.9/1.29	29.9-30.9/1.29	26.6/1.29	32.2/1.46	85.6/3.42	32.3/1.87	18.3/0.93	18.7/0.93
	xLAla?		49.3/4.37	17.8/1.38

There is only one chemically distinct structure:

SVGMWSMILES3D molIonize

 

CC(C)[C@H](CCCCCCCCCCCCC(=O)N[C@@H](C)C(=O)O)O[C@@H]1O[C@H](COC(=O)CCC(=O)O)[C@@H](O)[C@H](O)[C@H]1O

619.749 g/mol (C₃₀H₅₃NO₁₂)

Ieodoglucomides A (1) and B (2), unique glycolipopeptides consisting of an amino acid, a new fatty acid, a succinic acid, and a sugar, were isolated from a Marine-derived bacterium Bacillus licheniformis. The absolute stereochemistry of 1 and 2 was determined by deploying coupling constants, Marfey's and Mosher's methods, and literature reviews. Compounds 1 and 2 displayed moderate in vitro antimicrobial activity. Furthermore, ieodoglucomide B (2) exhibited cytotoxic activity against lung cancer and stomach cancer cell lines with GI(50) values of 25.18 and 17.78 μg/mL, respectively.

Bacillus licheniformis, antimicrobial activity, ieodoglucomides, glycolipopeptides, cytotoxic activity

13C NMR data:
Linkage	Residue	C1	C2	C3	C4	C5	C6	C7	C8	C9	C10	C11	C12	C13	C14	C15	C16	C17
2,14,6	xXSuc	174.1	26.64	26.99	175.9
2,14	bDGlcp	104.2	75.5	78.2	72.0	75.2	65.3
2	Subst	176.9	36.9	26.9	29.0-30.9	29.0-30.9	29.0-30.9	29.0-30.9	29.0-30.9	29.0-30.9	29.0-30.9	29.0-30.9	26.6	32.2	85.6	32.3	18.3	18.7
	xXGly	173.2	41.9


1H NMR data:
Linkage	Residue	H1	H2	H3	H4	H5	H6	H7	H8	H9	H10	H11	H12	H13	H14	H15	H16	H17
2,14,6	xXSuc	-	2.62	2.61	-
2,14	bDGlcp	4.29	3.19	3.33	3.28	3.40	4.18-4.44
2	Subst	-	2.25	1.62	1.29	1.29	1.29	1.29	1.29	1.29	1.29	1.29	1.29	1.45	3.43	1.88	0.93	0.93
	xXGly	-	3.89


1H/13C HSQC data:
Linkage	Residue	C1/H1	C2/H2	C3/H3	C4/H4	C5/H5	C6/H6	C7/H7	C8/H8	C9/H9	C10/H10	C11/H11	C12/H12	C13/H13	C14/H14	C15/H15	C16/H16	C17/H17
2,14,6	xXSuc		26.64/2.62	26.99/2.61	
2,14	bDGlcp	104.2/4.29	75.5/3.19	78.2/3.33	72.0/3.28	75.2/3.40	65.3/4.18-4.44
2	Subst		36.9/2.25	26.9/1.62	29.0-30.9/1.29	29.0-30.9/1.29	29.0-30.9/1.29	29.0-30.9/1.29	29.0-30.9/1.29	29.0-30.9/1.29	29.0-30.9/1.29	29.0-30.9/1.29	26.6/1.29	32.2/1.45	85.6/3.43	32.3/1.88	18.3/0.93	18.7/0.93
	xXGly		41.9/3.89

There is only one chemically distinct structure:

SVGMWSMILES3D molIonize

 

CC(C)[C@H](CCCCCCCCCCCCC(=O)NCC(=O)O)O[C@@H]1O[C@H](COC(=O)CCC(=O)O)[C@@H](O)[C@H](O)[C@H]1O

605.722 g/mol (C₂₉H₅₁NO₁₂)

Glycopeptidolipids (GPLs) are dominant cell surface molecules present in several non-tuberculous and opportunistic mycobacterial species. GPLs from Mycobacterium smegmatis are composed of a lipopeptide core unit consisting of a modified C26-C34 fatty acyl chain that is linked to a tetrapeptide (Phe-Thr-Ala-alaninol). The hydroxyl groups of threonine and terminal alaninol are further modified by glycosylations. Although chemical structures have been reported for 16 GPLs from diverse mycobacteria, there is still ambiguity in identifying the exact position of the hydroxyl group on the fatty acyl chain. Moreover, the enzymes involved in the biosynthesis of the fatty acyl component are unknown. In this study we show that a bimodular polyketide synthase in conjunction with a fatty acyl-AMP ligase dictates the synthesis of fatty acyl chain of GPL. Based on genetic, biochemical, and structural investigations, we determine that the hydroxyl group is present at the C-5 position of the fatty acyl component. Our retrobiosynthetic approach has provided a means to understand the biosynthesis of GPLs and also resolve the long-standing debate on the accurate structure of mycobacterial GPLs.

fatty acid, Mycobacteria, lipids, acyl carrier protein, polyketides, fatty acyl AMP ligase, hydroxylation, polyketide synthase

There is only one chemically distinct structure:

SVGMWSMILES3D molIonize

 

R1 = LIP
CO[1*]N[C@@H](Cc1ccccc1)C(=O)N[C@H](C(=O)N[C@@H](C)C(=O)NC(C)CO[C@@H]1O[C@@H](C)[C@H](O)[C@@H](O)[C@H]1O)[C@@H](C)O[C@@H]1O[C@@H](C)[C@@H](O)[C@@H](O)[C@H]1O

716.782 g/mol (C₃₂H₅₂RN₄O₁₄, R = underdetermined substituent(s), not counted in mol weight)