Catalyzes the conversion of GDP-D-mannose to GDP-4-dehydro-6-deoxy-D-mannose. GDP-alpha-D-mannose = GDP-4-dehydro-alpha-D-rhamnose + H2O Bacterial outer membrane biogenesis; lipopolysaccharide biosynthesis. Homotetramer. Belongs to the NAD(P)-dependent epimerase/dehydratase family. GDP-mannose 4,6-dehydratase subfamily.